Fluorination of porphyrin ß-periphery boosts nickel(II)-catalyzed hydrogen evolution reaction.

Tunichlorin, the naturally occurring chlorophyll cofactor containing Ni(II) ion, sets up a golden standard for designing the electrocatalysts for hydrogen evolution reaction (HER) via ß-peripheral modification. Besides the fine-tuning of the porphyrin ß-periphery such as adjusting the aromatics (the saturated level of tetrapyrrole) or installing hydroxyl group (hydrogen bond network) to enhance the catalytic HER efficiency, here we report that ß-fluorination of porphyrin is also an important approach to increase the reactivity of Ni(II) center. Benefiting the previously reported derivatization of ß-fluorinated porpholactones, we constructed a ß-fluorinated tunichlorin mimic (6). Compared with the non-fluorinated analogs (1, 3, and 5), we found that 2, 4, and 6 exhibit significant electrocatalytic HER reactivity acceleration (in terms of turnover frequencies, TOF, s-1) of ca. 37, 170, 133-fold, respectively. Mechanism studies suggested that ß-fluorination negatively shifts the metal complexes' reduction potentials and accelerates the electron transfer process, both contributing to the boosting of HER reaction. Notably, 6 showed an 890-fold increase of TOFs than 1, demonstrating the combining advantages of the of fluorination, hydrogenation, and hydroxylation at porphyrin ß-periphery.

Effects of Exercise Habits and Gender on Sports e-Learning Behavior: Evidence from an Eye-Tracking Study.

Background/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology. Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment. Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P<0.05), a shorter average fixation duration (P<0.05), a smaller average pupil diameter (P<0.05), and a lower subjective cognitive load (P<0.05) and better learning outcome (P<0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05). Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.

Metal nutrition and transport in the process of symbiotic nitrogen fixation.

Symbiotic nitrogen fixation (SNF) facilitated by the interaction between legumes and rhizobia is a well-documented and eco-friendly alternative to chemical nitrogen fertilizers. Host plants obtain fixed nitrogen from rhizobia by providing carbon and mineral nutrients. These mineral nutrients, which are mostly in the form of metal ions, are implicated in various stages of the SNF process. This review describes the functional roles played by metal ions in nodule formation and nitrogen fixation and specifically addresses their transport mechanisms and associated transporters within root nodules. Future research directions and potential strategies for enhancing SNF efficiency are also discussed.

Exposure to pesticides and risk of colorectal cancer: A systematic review and meta-analysis.

Colorectal cancer (CRC) is a widespread malignancy worldwide, and its relationship with pesticide exposure remains inconclusive. This study aims to elucidate the relationship between pesticide exposure and the risk of colon, rectal, or CRC, focusing on specific pesticide groups. We conducted an extensive literature search for peer-reviewed studies published up to March 31, 2023. Summary risk ratios (RR) and their corresponding 95% confidence intervals (CI) were calculated using stratified random-effects meta-analyses, taking into account different types of exposure and outcomes, and various exposed populations and pesticide subgroups. This approach aimed to address the substantial heterogeneity observed across the literature. We also assessed heterogeneity and potential small-study effects to ensure the robustness of our findings. From the 50 studies included in this review, 33 contributed to the meta-analysis. Our results indicate a significant association between herbicide exposure and colon cancer in both lifetime-days (LDs) (RR = 1.20; 95% CI = 1.01-1.42) and intensity-weighted lifetime-days (IWLDs) (RR = 1.29, 95% CI = 1.12-1.49) exposure. Similarly, insecticide exposure was associated with an increased risk of colon cancer in IWLDs (RR = 1.32; 95% CI = 1.02-1.70) exposure, and rectal cancer in any versus never exposure (RR = 1.21; 95% CI = 1.07-1.36), IDs (RR = 1.86; 95% CI = 1.30-2.67) and IWLDs (RR = 1.70; 95% CI = 1.03-2.83) exposure. While these findings suggest significant associations of herbicide and insecticide exposure with colon and rectal cancer, respectively, further research is needed to explore the impact of other pesticide groups and deepen our understanding of pesticide exposure. These results have important implications for policymakers and regulators, underscoring the need for stricter supervision and regulation of pesticide use to mitigate CRC risk.

Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids.

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

Phosphine Catalysis of the Fluorination of Unactivated Tertiary Alkyl Chlorides under Mild and Convenient Conditions.

Due to the significance of organofluorine compounds in disciplines ranging from medicine to agriculture to materials science, the invention of new methods for the creation of carbon-fluorine bonds is an important objective. Among the underdeveloped dimensions in this area are the fluorination of hindered alkyl halides (particularly chlorides) and the discovery of catalysts for such fluorination processes. Herein, we report a mild method for the fluorination of unactivated tertiary alkyl chlorides (and bromides), catalyzed by inexpensive PPh3. This straightforward process is compatible with a range of hindered electrophiles and a variety of functional groups.

Neural representation of gestalt grouping and attention effect in human visual cortex.

BACKGROUND: The brain aggregates meaningless local sensory elements to form meaningful global patterns in a process called perceptual grouping. Current brain imaging studies have found that neural activities in V1 are modulated during visual grouping. However, how grouping is represented in each of the early visual areas, and how attention alters these representations, is still unknown. NEW METHOD: We adopted MVPA to decode the specific content of perceptual grouping by comparing neural activity patterns between gratings and dot lattice stimuli which can be grouped with proximity law. Furthermore, we quantified the grouping effect by defining the strength of grouping, and assessed the effect of attention on grouping. RESULTS: We found that activity patterns to proximity grouped stimuli in early visual areas resemble these to grating stimuli with the same orientations. This similarity exists even when there is no attention focused on the stimuli. The results also showed a progressive increase of representational strength of grouping from V1 to V3, and attention modulation to grouping is only significant in V3 among all the visual areas. COMPARISON WITH EXISTING METHODS: Most of the previous work on perceptual grouping has focused on how activity amplitudes are modulated by grouping. Using MVPA, the present work successfully decoded the contents of neural activity patterns corresponding to proximity grouping stimuli, thus shed light on the availability of content-decoding approach in the research on perceptual grouping. CONCLUSIONS: Our work found that the content of the neural activity patterns during perceptual grouping can be decoded in the early visual areas under both attended and unattended task, and provide novel evidence that there is a cascade processing for proximity grouping through V1 to V3. The strength of grouping was larger in V3 than in any other visual areas, and the attention modulation to the strength of grouping was only significant in V3 among all the visual areas, implying that V3 plays an important role in proximity grouping.

Differential effects of social isolation on oligodendrocyte development in different brain regions: insights from a canine model.

Social isolation (SI) exerts diverse adverse effects on brain structure and function in humans. To gain an insight into the mechanisms underlying these effects, we conducted a systematic analysis of multiple brain regions from socially isolated and group-housed dogs, whose brain and behavior are similar to humans. Our transcriptomic analysis revealed reduced expression of myelin-related genes specifically in the white matter of prefrontal cortex (PFC) after SI during the juvenile stage. Despite these gene expression changes, myelin fiber organization in PFC remained unchanged. Surprisingly, we observed more mature oligodendrocytes and thicker myelin bundles in the somatosensory parietal cortex in socially isolated dogs, which may be linked to an increased expression of ADORA2A, a gene known to promote oligodendrocyte maturation. Additionally, we found a reduced expression of blood-brain barrier (BBB) structural components Aquaporin-4, Occludin, and Claudin1 in both PFC and parietal cortices, indicating BBB disruption after SI. In agreement with BBB disruption, myelin-related sphingolipids were increased in cerebrospinal fluid in the socially isolated group. These unexpected findings show that SI induces distinct alterations in oligodendrocyte development and shared disruption in BBB integrity in different cortices, demonstrating the value of dogs as a complementary animal model to uncover molecular mechanisms underlying SI-induced brain dysfunction.

Enantioselective Synthesis of cis-Decalins by Merging the Birch Reduction and Inverse-Electron-Demand Diels-Alder Reaction.

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis-decalin scaffolds. Enabled by a well-modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis-decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)-occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3-cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2- and/or C3-substituted 1,4-cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels-Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities.

Effectiveness of exercise intervention on improving fundamental motor skills in children with autism spectrum disorder: a systematic review and meta-analysis.

Background: Autism spectrum disorder (ASD) is a severe public health concern, and most of the children with ASD experience a substantial delay in FMS. This study aimed to investigate the effectiveness of exercise interventions in improving FMS in children with ASD, and provide evidence to support the scientific use of exercise interventions in practice. Methods: We searched seven online databases (PubMed, Scopus, Web of Science, Embase, EBSCO, Clinical Trials, and The Cochrane Library) from inception to May 20, 2022. We included randomized control trials of exercise interventions for FMS in children with ASD. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database Scale. Stata 14.0 software was used for meta-analysis, forest plotting, subgroup analysis, heterogeneity analysis, and meta-regression. Results: Thirteen studies underwent systematic review (541 participants), of which 10 underwent meta-analysis (297 participants). Overall, exercise interventions significantly improved overall FMS in children with ASD. Regarding the three categories of FMS, exercise interventions significantly improved LMS (SMD = 1.07; 95% CI 0.73 to 1.41, p < 0.001), OCS (SMD = 0.79; 95% CI 0.32 to 1.26, p = 0.001), and SS (SMD = 0.72; 95% CI 0.45 to 0.98, p < 0.0001). Conclusion: exercise interventions can effectively improve the FMS of children with ASD. The effects on LMS are considered as large effect sizes, while the effects on OCS and SS are considered as moderate effect sizes. These findings can inform clinical practice. Systematic review registration: https://inplasy.com/inplasy-2022-12-0013/.

Diffusion prepared pseudo-continuous arterial spin labeling reveals blood-brain barrier dysfunction in patients with CADASIL.

OBJECTIVES: Diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of the blood-brain barrier (BBB). We aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and to analyze the association between the BBB water exchange rate and MRI/clinical features of these patients. METHODS: Forty-one patients with CADASIL and thirty-six age- and sex-matched controls were scanned with DP-pCASL MRI to estimate the BBB water exchange rate (kw). The MRI lesion burden, the modified Rankin scale (mRS), and the neuropsychological scales were also examined. The association between kw and MRI/clinical features was analyzed. RESULTS: Compared with that in the controls, kw in patients with CADASIL was decreased at normal-appearing white matter (NAWM) (t = - 4.742, p < 0.001), cortical gray matter (t = - 5.137, p < 0.001), and deep gray matter (t = - 3.552, p = 0.001). After adjustment for age, gender, and arterial transit time, kw at NAWM was negatively associated with the volume of white matter hyperintensities (ß = - 0.754, p = 0.001), whereas decreased kw at NAWM was independently associated with an increased risk of abnormal mRS scale (OR = 1.058, 95% CI: 1.013-1.106, p = 0.011) in these patients. CONCLUSIONS: This study found that the BBB water exchange rate was decreased in patients with CADASIL. The decreased BBB water exchange rate was associated with an increased MRI lesion burden and functional dependence of the patients, suggesting the involvement of BBB dysfunction in the pathogenesis of CADASIL. CLINICAL RELEVANCE STATEMENT: DP-pCASL reveals BBB dysfunction in patients with CADASIL. The decreased BBB water exchange rate is associated with MRI lesion burden and functional dependence, indicating the potential of DP-pCASL as an evaluation method for disease severity. KEY POINTS: • DP-pCASL reveals blood-brain barrier dysfunction in patients with CADASIL. • Decreased BBB water exchange rate, an indicator of BBB dysfunction detected by DP-pCASL, was associated with MRI/clinical features of patients with CADASIL. • DP-pCASL can be used as an evaluation method to assess the severity of disease in patients with CADASIL.

AllenDigger, a Tool for Spatial Expression Data Visualization, Spatial Heterogeneity Delineation, and Single-Cell Registration Based on the Allen Brain Atlas.

Spatial transcriptomics can be used to capture cellular spatial organization and has facilitated new insights into different biological contexts, including developmental biology, cancer, and neuroscience. However, its wide application is still hindered by its technical challenges and immature data analysis methods. Allen Brain Atlas (ABA) provides a great source for spatial gene expression throughout the mouse brain at various developmental stages with in situ hybridization image data. To the best of our knowledge, the portal developed to access spatial expression data is not very useful to biologists. Here, we developed a toolkit to collect and preprocess expression data from the ABA and allow a friendlier query to visualize the spatial distribution of genes of interest, characterize the spatial heterogeneity of the brain, and register cells from single-cell transcriptomics data to fine anatomical brain regions via machine learning methods with high accuracy. AllenDigger will be very helpful to the community in precise spatial gene expression queries and add extra spatial information to further interpret the scRNA-seq data in a cost-effective manner.

Phenotypes and genetic etiology of spontaneous polycystic kidney and liver disease in cynomolgus monkey.

Introduction: Polycystic kidney disease (PKD) is a common autosomal dominant or recessive genetic disease, often accompanied by polycystic liver disease (PLD). Many cases of PKD in animals have been reported. However, little is known about the genes that cause PKD in animals. Methods: In this study, we evaluated the clinical phenotypes of PKD in two spontaneously aged cynomolgus monkeys and explored the genetic etiology using whole-genome sequencing (WGS). Ultrasonic and histological consequences were further investigated in PKD- and PLD-affected monkeys. Results: The results indicated that the kidneys of the two monkeys had varying degrees of cystic changes, and the renal cortex was thinned and accompanied by fluid accumulation. As for hepatopathy, inflammatory cell infiltration, cystic effusion, steatosis of hepatocytes, and pseudo-lobular were found. Based on WGS results, the variants of PKD1:(XM_015442355: c.1144G>C p. E382Q) and GANAB: (NM_001285075.1: c.2708T>C/p. V903A) are predicted to be likely pathogenic heterozygous mutations in PKD- and PLD-affected monkeys. Discussion: Our study suggests that the cynomolgus monkey PKD and PLD phenotypes are very similar to those in humans, and are probably caused by pathogenic genes homologous to humans. The results indicate that cynomolgus monkeys can be used as the most appropriate animal model for human PKD pathogenesis research and therapeutic drug screening.

Oncogenic FLT3 internal tandem duplication activates E2F1 to regulate purine metabolism in acute myeloid leukaemia.

Oncogene FLT3 internal tandem duplication (FLT3-ITD) mutation accounts for 30 % of acute myeloid leukaemia (AML) cases and induces transformation. Previously, we found that E2F transcription factor 1 (E2F1) was involved in AML cell differentiation. Here, we reported that E2F1 expression was aberrantly upregulated in AML patients, especially in AML patients carrying FLT3-ITD. E2F1 knockdown inhibited cell proliferation and increased cell sensitivity to chemotherapy in cultured FLT3-ITD-positive AML cells. E2F1-depleted FLT3-ITD+ AML cells lost their malignancy as shown by the reduced leukaemia burden and prolonged survival in NOD-PrkdcscidIl2rgem1/Smoc mice receiving xenografts. Additionally, FLT3-ITD-driven transformation of human CD34+ hematopoietic stem and progenitor cells was counteracted by E2F1 knockdown. Mechanistically, FLT3-ITD enhanced the expression and nuclear accumulation of E2F1 in AML cells. Further study using chromatin immunoprecipitation-sequencing and metabolomics analyses revealed that ectopic FLT3-ITD promoted the recruitment of E2F1 on genes encoding key enzymatic regulators of purine metabolism and thus supported AML cell proliferation. Together, this study demonstrates that E2F1-activated purine metabolism is a critical downstream process of FLT3-ITD in AML and a potential target for FLT3-ITD+ AML patients.

Oral delivery of nucleic acid therapeutics: Challenges, strategies, and opportunities.

In recent decades, advances in chemical synthesis and delivery systems have accelerated the development of therapeutic nucleic acids, several of which have been approved by the Us Food and Drug Administration (FDA). Oral nucleic acid delivery is preferred because of its simplicity and patient compliance, but it still presents distinct challenges. The negative charge, hydrophilicity, and large molecular weight of nucleic acids combined with in vivo gastrointestinal (GI) barriers (e.g., acidic pH, enzymes, mucus, and intestinal epithelial cells) severely hinder their delivery efficacy. Recently, various nanoparticles (NPs), ranging from polymeric to lipid-based (L)NPs and extracellular vesicles (EVs), have been extensively explored to address these obstacles. In this review, we describe the physiological barriers in the GI tract and summarize recent advances in NP-based oral nucleic acid therapeutics.

ADCK1 is a potential therapeutic target of osteosarcoma.

We here showed that ADCK1 (AarF domain-containing kinase 1), a mitochondrial protein, is upregulated in human osteosarcoma (OS) tissues and OS cells. In primary and established OS cells, ADCK1 shRNA or CRISPR/Cas9-induced ADCK1 knockout (KO) remarkably inhibited cell viability, proliferation and migration, and provoked apoptosis activation. Conversely, ectopic ADCK1 overexpression exerted pro-cancerous activity by promoting OS cell proliferation and migration. ADCK1 depletion disrupted mitochondrial functions in OS cells and induced mitochondrial membrane potential reduction, ATP depletion, reactive oxygen species production. Significantly, ADCK1 silencing augmented doxorubicin-induced apoptosis in primary OS cells. mTOR activation is important for ADCK1 expression in OS cells. The mTOR inhibitors, rapamycin and AZD2014, as well as mTOR shRNA, potently decreased ADCK1 expression in primary OS cells. In nude mice, the growth of subcutaneous pOS-1 xenografts was largely inhibited when bearing ADCK1 shRNA or ADCK1 KO construct. Moreover, ADCK1 KO largely inhibited pOS-1 xenograft in situ growth in proximal tibia of nude mice. ADCK1 depletion, apoptosis activation and ATP reduction were detected in pOS-1 xenografts bearing ADCK1 shRNA or ADCK1 KO construct. Together, the mitochondrial protein ADCK1 is required for OS cell growth and is a novel therapeutic target of OS.

Investigating the mechanical effect of the sagittal angle of the cervical facet joint on the cervical intervertebral disc.

Background: Facet tropism is defined as the asymmetry between the left and right facet joints relative to the sagittal plane. Published clinical studies have found that facet tropism is associated with cervical disc herniation. However, the relationship between the facet orientation and the side of cervical disc herniation remains controversial. Therefore, this study used the finite-element technique to investigate the biomechanical effects of the sagittal angle of the cervical facet joints on the cervical intervertebral disc. Objective: The biomechanical effects of the sagittal angle of the cervical facet joint on the cervical disc and facet joint were investigated using the finite-element technique. Methods: The finite-element model was constructed using computed tomography scans of a 26-year-old female volunteer. First, a cervical model was constructed from C3 to C7. The model was verified using data from previously published studies. Second, the facet orientation at the C5-C6 level was altered to simulate different sagittal angles of cervical facet joints. Five models, F70, F80, F90, F100, and F110, were simulated with different facet joint orientations (70°, 80°, 90°, 100°, and 110° facet joint angles at the left side, respectively, and 90° facet joint angles at the right side) at the C5-C6 facet joints. In each model, annular fibres stress and facet cartilage pressure were studied under six pure moments and two combined moments. Results: Comparing the stress of the annulus fibres in flexion combined with right axial rotation and in flexion combined with left axial rotation in the same model, no difference in the maximum stress of the annulus fibres was noted between these two different moments in the F90 model, whereas differences of 12.80%, 8.84%, 14.95% and 33.32% were noted in the F70, F80, F100 and F110 models, respectively. The same trend was observed when comparing the maximum stress of the annulus fibres in each model during left and right axial rotation. No differences in annular fibres stress and facet cartilage pressure were noted among the five models in flexion, extension, lateral bending, left axial rotation, and flexion combined with left axial rotation in this study. However, compared with the F70 model in flexion combined with right axial rotation, the annulus fibres stress of the F80, F90, F100, and F110 models increased by 5.53%, 13.03%, 35.04%, and 72.94%, respectively, and the pressure of the left facet joint of these models decreased by 5.65%, 12.10%, 18.41%, and 25.74%, respectively. The same trend was observed in the right axial moment. Conclusion: Facet tropism leads to unbalanced stress distribution on the annulus fibres at the cervical intervertebral disc. The greater the sagittal angle of the facet joint, the greater the annular fibres stress on this side. We hypothesised that the side with the larger sagittal angle of the facet joint exhibits a greater risk of disc herniation.

Two central circadian oscillators OsPRR59 and OsPRR95 modulate magnesium homeostasis and carbon fixation in rice.

Photosynthesis, which provides oxygen and energy for all living organisms, is circadian regulated. Photosynthesis-associated metabolism must tightly coordinate with the circadian clock to maximize the efficiency of the light-energy capture and carbon fixation. However, the molecular basis for the interplay of photosynthesis and the circadian clock is not fully understood, particularly in crop plants. Here, we report two central oscillator genes of circadian clock, OsPRR95 and OsPRR59 in rice, which function as transcriptional repressors to negatively regulate the rhythmic expression of OsMGT3 encoding a chloroplast-localized Mg2+ transporter. OsMGT3-dependent rhythmic Mg fluctuations modulate carbon fixation and consequent sugar output in rice chloroplasts. Furthermore, sugar triggers the increase of superoxide, which may act as a feedback signal to positively regulate the expression of OsPRR95 and OsPRR59. Taken together, our results reveal a negative-feedback loop that strengthens the crosstalk between photosynthetic carbon fixation and the circadian clock, which may improve plan adaptation and performance in fluctuating environments.

Shape-directed drug release and transport of erythrocyte-like nanodisks augment chemotherapy.

Nanoparticle shape has been recognized as a crucial parameter to affect the transport across various biological barriers, but its impact on drug release and the resulting therapeutic efficacy is less understood. Inspired by erythrocytes with shape-facilitated oxygen-carrying and penetrating abilities, we constructed artificial erythrocyte-like nanoparticles (RNDs) by wrapping discoidal mesoporous silica nanoparticles with red blood cell membrane. We observed that, compared with their spherical and rod-shaped counterparts with monotonic drug release profiles, RNDs displayed an on-demand drug release pattern mimicking natural erythrocytes, that is, they could rapidly release loaded oxygen and doxorubicin (DOX) in hypoxic condition but were relatively stable in high oxygen areas. Besides, the discoidal shape also endowed RNDs with facilitated transport capability in tumor extracellular matrix, contributing to increased tumor permeability. In tumor models, systemically administrated RNDs efficiently infiltrate throughout tumor tissue, successfully relieve tumor hypoxia, and further altered the cancer cell cycle status from G1 to G2 phase, enhancing cancer cell sensitivity to DOX correlated with improved chemotherapy efficacy. In contrast, nanospheres show hampered permeability, and nanorods suffer from insufficient intratumoral drug accumulation. These findings can offer guidelines for the use of particle shape as a design criterion to control drug release, transportation, and therapeutics delivery.