Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer.

Currently, only 20-40% of cancer patients benefit from immune checkpoint inhibitors. Understanding the mechanisms underlying the immunosuppressive tumor microenvironment (TME) and characterizing dynamic changes in the immunological landscape during treatment are critical for improving responsiveness to immunotherapy. Here, we identified JNK signaling in cancer-associated fibroblasts (CAFs) as a regulator of the immunosuppressive tumor microenvironment. Single-cell RNA sequencing of bladder cancer treated with a JNK inhibitor revealed enhanced cytotoxicity and effector functions of CD8+ T cells. In untreated tumors, CAFs interacted frequently with CD8+ T cells and mediated their exhaustion. JNK inhibition abrogated the immunosuppression function of CAFs by downregulating the expression of TSLP, thereby restoring CD8+ T cell cytotoxicity. In addition, blockade of CAF-derived TSLP in combination with anti-PD1 treatment promoted tumor elimination by CD8+ T cells in vivo. Collectively, these results indicate that JNK signaling plays an important immunosuppressive role in the tumor microenvironment by promoting expression of TSLP in CAFs and suggest that inhibiting JNK signaling could be a promising immunotherapeutic strategy for cancer treatment.

Prevalence and risk factors of sleep disorders in inflammatory bowel disease: a cross-sectional study.

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.

Discovery of SARS-CoV-2 papain-like protease (PLpro) inhibitors with efficacy in a murine infection model.

Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PLpro inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

Effects of Acremonium terricola Culture on Lactation Performance, Immune Function, Antioxidant Capacity, and Intestinal Flora of Sows.

This study aimed to determine the effects of different doses of Acremonium terricola culture (ATC) on lactation performance, immune function, antioxidant capacity, and intestinal flora of sows. Forty-five Landrace sows (3-6 parity) were randomly assigned to the following three treatments from 85 days of gestation to 21 days after farrowing: a control diet (CON, basal diet), a low-dose Acremonium terricola culture diet (0.2% ATC, basal diet + 0.2% ATC), and a high-dose Acremonium terricola culture diet (0.4% ATC, basal diet + 0.4% ATC). Compared with the CON group, the supplementation of 0.2% ATC increased the average daily milk yield of sows by 4.98%, increased milk fat, total solids, and freezing point depression on day 1 postpartum (p < 0.05), increased serum concentration of Triiodothyronine, Thyroxin, and Estradiol on day 21 postpartum (p < 0.05). Compared with the CON group, the supplementation of 0.4% ATC increased the average daily milk yield of sows by 9.38% (p < 0.05). Furthermore, the supplementation of 0.2% ATC increased serum concentration of IgG, IgM, and IFN-γ, CD4 on day 1 postpartum (p < 0.05) and increased serum concentration of immunoglobulin A ( IgA), immunoglobulin G (IgG), immunoglobulin M ( IgM), complement 3 (C3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), interferon-γ (IFN-γ) on day 21 postpartum (p < 0.05), while the supplementation of 0.4% ATC reduced serum concentration of IL-2 on day 21 postpartum (p < 0.05). Moreover, the supplementation of 0.4% ATC significantly increased serum concentration of catalase (CAT) (p < 0.05). Additionally, the supplementation of ATC affected the relative abundance of the intestinal flora at different taxonomic levels in sows and increased the abundance of beneficial bacteria such as in the norank_f__Eubacterium_coprostanoligenes group, Eubacterium_coprostanoligenes group, and Lachnospiraceae_XPB1014 group of sows, while reducing the abundance of harmful bacteria such as Phascolarctobacterium and Clostridium_sensu_stricto_1. These data revealed that the supplementation of ATC during late gestation and lactation can improve lactation performance, immune function, antioxidant capacity, and the gut microbiota. Compared with supplementation of 0.4% ATC, 0.2% ATC enhances the levels of thyroid-related hormones, specific antibodies, and cytokines in serum, promotes the diversity of beneficial gut microbiota, beneficial bacteria in the intestine, reduces the population of harmful bacteria, and thereby bolsters the immunity of sows. Hence, 0.2% ATC is deemed a more optimal concentration.

The impact of tea consumption on the risk of depression: A Mendelian randomization and Bayesian weighting algorithm study.

BACKGROUND AND OBJECTIVES: The precise impact of tea consumption on the risk of depression remains unclear. This study aimed to explore the relationship between the consumption patterns of tea and the likelihood of depression onset, utilizing a two-sample Mendelian randomization (MR) methodology. METHODS AND STUDY DESIGN: We utilized available genome-wide association study (GWAS) datasets on tea intake and depressive disorders. To investigate the causal relationship between tea consumption and depression, we employed a set of two-sample Mendelian Randomization (MR) methods. These included the inverse-variance weighted (IVW) analysis, weighted median approach, and MR-Egger regression. Additionally, we utilized MR-PRESSO and the MR-Egger intercept test for the detection of pleiotropic effects. To ensure the robustness and consistency of our findings, a sensitivity analysis was carried out, applying the 'leave-one-out' strategy. The Bayesian weighted Mendelian randomization (BWMR) was employed to conduct additional testing on the obtained results. RESULTS: The study's outcomes revealed a causal association between increased tea intake and an increased risk of depression (Inverse-Variance Weighted Analysis: Odds Ratio [OR] = 1.029, 95% Confidence Interval [CI]: 1.003-1.055, p = 0.027). This was observed despite variations in instrumental variables and the nonexistence of horizontal pleiotropy. Furthermore, the robustness of our Mendelian Randomization investigation was affirmed through the implementation of the 'leave-one-out' method in our sensitivity analysis. The findings from BWMR were in line with those obtained from IVW (BWMR: OR=1.030, 95% CI: 1.003-1.057, p = 0.029). CONCLUSIONS: The results from this study indicate a substantial and positive causal link between the regularity of tea drinking and the risk of depression onset.

CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN/AKT signaling phosphorylation and neutrophil chemotaxis.

BACKGROUND: Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. METHODS: We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. RESULTS: We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. CONCLUSIONS: Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.

Combined Inhibition of PI3K and STAT3 signaling effectively inhibits bladder cancer growth.

Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.

Biodegradation Characteristics and Mechanism of Aflatoxin B1 by Bacillus amyloliquefaciens from Enzymatic and Multiomics Perspectives.

Aflatoxin B1 (AFB1), a mycotoxin and natural carcinogen, commonly contaminates cereals and animal feeds, posing serious health risks to human and animal. In this study, Bacillus amyloliquefaciens ZG08 isolated from kimchi could effectively remove 80.93% of AFB1 within 72 h at 37 °C and pH 7.0. Metabolome and transcriptome analysis showed that metabolic processes including glycerophospholipid metabolism and amino acid metabolism were most affected in B. amyloliquefaciens ZG08 exposed to AFB1. The adaptation mechanism likely involved activation of the thioredoxin system to restore intracellular redox equilibrium. The key genes, tpx and gldA, overexpressed in Escherichia coli BL21, achieved degradation rates of 60.15% and 47.16% for 100 µg/kg AFB1 under optimal conditions of 37 °C and pH 8.0 and 45 °C and pH 7.0, respectively. The degradation products, identified as AFD1, were less cytotoxic than AFB1 in HepG2 cells. These findings suggest potential strategies for utilizing probiotics and engineered enzymes in AFB1 detoxification.

TET1 mediated m5C modification of RelB aggravates cerebral ischemia/reperfusion-induced neuroinflammation through regulating microglia polarization.

Microglia mediated neuroinflammation is one of the major contributors to brain damage in cerebral ischemia reperfusion injury (CI/RI). Recently, RNA modification was found to contribute to the regulation of microglia polarization and the subsequent development of cerebral I/R neuroinflammation. Herein, we investigated the effect and mechanism of m5C RNA modification in the microglia induced CI/RI neuroinflammation. We found that the m5C RNA modification levels decreased in the primary microglia isolated from a mouse model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) and the BV2 microglial cells subjected to oxygen-glucose deprivation and reoxygenation (OGD/R), and this change was accompanied by an increase in the M1/M2 polarization ratio. Furthermore, the expression of m5C demethylase TET1 in microglia increased, which promoted M1 polarization but impeded M2 polarization. Mechanistically, the higher TET1 expression decreased the m5C modification level of RelB and enhanced its mRNA stability, which subsequently increased the M1/M2 polarization ratio. In conclusion, this study provides insight into the role of m5C RNA modification in the pathogenesis of cerebral I/R neuroinflammation and may deepen our understanding on clinical therapy targeting the TET1-RelB axis.

Transcription-related metabolic regulation in grafted lemon seedlings under magnesium deficiency stress.

Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA3, JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe.

Mechanical pretreatment of typical agricultural biomass on shape characterization and NO emissions during combustion.

The impact of mechanical pretreatment of corn straw (CS), pea straw (PS), and wheat straw (WS), on shape characterization and NO emissions during combustion were investigated in this research. Particle size ranges were obtained and characterized their shape factors using Image J correction. The thermal properties and NO emissions of the different-sized particles were investigated by TG-MS and fixed-bed reactor. Compared with CS and PS, WS is more likely to break into smaller particles due to its moderate strength. Amine-N completely disappeared after pyrolysis, whereas pyrrolic-N and pyridinic-N were the main N functionalities in char-N. During the volatile burning stage, the maximum peak of NO concentration was 270, 354 and 311 ppm for CS, PS and WS, respectively. NO was detected at a steady level during the semicoke combustion stage, and the duration increased with particle size. The NO concentration decreased sharply in a short duration during the fixed carbon combustion stage.

ACC SYNTHASE4 inhibits gibberellin biosynthesis and FLOWERING LOCUS T expression during citrus flowering.

Flowering is an essential process in fruit trees. Flower number and timing have a substantial impact on the yield and maturity of fruit. Ethylene and gibberellin (GA) play vital roles in flowering, but the mechanism of coordinated regulation of flowering in woody plants by GA and ethylene is still unclear. In this study, a lemon (Citrus limon L. Burm) 1-aminocyclopropane-1-carboxylic acid synthase gene (CiACS4) was overexpressed in Nicotiana tabacum and resulted in late flowering and increased flower number. Further transformation of citrus revealed that ethylene and starch content increased, and soluble sugar content decreased in 35S:CiACS4 lemon. Inhibition of CiACS4 in lemon resulted in effects opposite to that of 35S:CiACS4 in transgenic plants. Overexpression of the CiACS4-interacting protein ETHYLENE RESPONSE FACTOR3 (CiERF3) in N. tabacum resulted in delayed flowering and more flowers. Further experiments revealed that the CiACS4-CiERF3 complex can bind the promoters of FLOWERING LOCUS T (CiFT) and GOLDEN2-LIKE (CiFE) and suppress their expression. Moreover, overexpression of CiFE in N. tabacum led to early flowering and decreased flowers, and ethylene, starch, and soluble sugar contents were opposite to those in 35S:CiACS4 transgenic plants. Interestingly, CiFE also bound the promoter of CiFT. Additionally, GA3 and 1-aminocyclopropanecarboxylic acid (ACC) treatments delayed flowering in adult citrus, and treatment with GA and ethylene inhibitors increased flower number. ACC treatment also inhibited the expression of CiFT and CiFE. This study provides a theoretical basis for the application of ethylene to regulate flower number and mitigate the impacts of extreme weather on citrus yield due to delayed flowering.

Transcriptomic analysis of the longissimus thoracis muscle in pigs has identified molecular regulatory patterns associated with meat quality.

Meat quality is a critical aspect of pig breeding. In addition to genetics, meat quality is also influenced by nutritional and environmental factors. In this study, three pig breeds, Shengxianhua, Jiaxing, and Qinglian Black (SXH, JXB and QLB), were used as experimental animals. Transcriptional analysis was performed on the longissimus thoracis (LT) muscle to investigate variations in intramuscular fat (IMF), inosine monophosphate (IMP), amino acids, and muscle fiber morphology across different breeds. Ingenuity canonical pathway analysis (IPA) identified biological processes and key driver genes related to metabolism and muscle development. Additionally, weighted gene co-expression network analysis (WGCNA) revealed gene modules associated with IMP. KEGG and GO analyses identified specific biological processes and signaling pathways related to IMP, including the Oxidative Phosphorylation pathway and rRNA Metabolic Processes. These findings provide novel insights into the molecular regulatory mechanisms underlying meat quality variations among pig breeds.

Transgenerational inheritance of adrenal steroidogenesis inhibition induced by prenatal dexamethasone exposure and its intrauterine mechanism.

BACKGROUND: Adrenal gland is the synthesis and secretion organ of glucocorticoid, which is crucial to fetal development and postnatal fate. Recently, we found that prenatal dexamethasone exposure (PDE) could cause adrenal dysfunction in offspring rats, but its multigenerational genetic effects and related mechanisms have not been reported. METHODS: The PDE rat model was established, and female filial generation 1 (F1) rats mate with wild males to produce the F2, the same way for the F3. Three generation rats were sacrificed for the related detection. SW-13 cells were used to clarify the epigenetic molecular mechanism. RESULTS: This study confirmed that PDE could activate fetal adrenal glucocorticoid receptor (GR). The activated GR, on the one hand, up-regulated Let-7b (in human cells) to inhibit steroidogenic acute regulatory protein (StAR) expression directly; on the other hand, down-regulated CCCTC binding factor (CTCF) and up-regulated DNA methyltransferase 3a/3b (Dnmt3a/3b), resulting in H19 hypermethylation and low expression. The decreased interaction of H19 and let-7 can further inhibit adrenal steroidogenesis. Additionally, oocytes transmitted the expression change of H19/let-7c axis to the next generation rats. Due to its genetic stability, F2 generation oocytes indirectly exposed to dexamethasone also inhibited H19 expression, which could be inherited to the F3 generation. CONCLUSIONS: This cascade effect of CTCF/H19/Let-7c ultimately resulted in the transgenerational inheritance of adrenal steroidogenesis inhibition of PDE offspring. This study deepens the understanding of the intrauterine origin of adrenal developmental toxicity, and it will provide evidence for the systematic analysis of the transgenerational inheritance effect of acquired traits induced by PDE. Video Abstract.

Multi-Omics Reveals the Effect of Crossbreeding on Some Precursors of Flavor and Nutritional Quality of Pork.

Over the last several decades, China has continuously introduced Duroc boars and used them as breeding boars. Although this crossbreeding method has increased pork production, it has affected pork quality. Nowadays, one of the primary goals of industrial breeding and production systems is to enhance the quality of meat. This research analyzed the molecular mechanisms that control the quality of pork and may be used as a guide for future efforts to enhance meat quality. The genetic mechanisms of cross-breeding for meat quality improvement were investigated by combining transcriptome and metabolome analysis, using Chinese native Jiaxing black (JXB) pigs and crossbred Duroc × Duroc × Berkshire × JXB (DDBJ) pigs. In the longissimus Dorsi muscle, the content of inosine monophosphate, polyunsaturated fatty acid, and amino acids were considerably higher in JXB pigs in contrast with that of DDBJ pigs, whereas DDBJ pigs have remarkably greater levels of polyunsaturated fatty acids than JXB pigs. Differentially expressed genes (DEGs) and differential metabolites were identified using transcriptomic and metabolomic KEGG enrichment analyses. Differential metabolites mainly include amino acids, fatty acids, and phospholipids. In addition, several DEGs that may explain differences in meat quality between the two pig types were found, including genes associated with the metabolism of lipids (e.g., DGKA, LIPG, and LPINI), fatty acid (e.g., ELOVL5, ELOVL4, and ACAT2), and amino acid (e.g., SLC7A2, SLC7A4). Combined with the DEGS-enriched signaling pathways, the regulatory mechanisms related to amino acids, fatty acids, and phospholipids were mapped. The abundant metabolic pathways and DEGs may provide insight into the specific molecular mechanism that regulates meat quality. Optimizing the composition of fatty acids, phospholipids, amino acids, and other compounds in pork is conducive to improving meat quality. Overall, these findings will provide useful information and further groundwork for enhancing the meat quality that may be achieved via hybrid breeding.

A novel dual-channel immunochromatographic strip using up-conversion nanoparticles for simultaneous detection of AFB1 and ZEN in maize.

Due to universal contamination and synergistic toxicity of multiple mycotoxins in foodstuff, reliable and high-throughput detection methods for multiple mycotoxins are urgently needed in corn products. In this study, a novel dual-channel immunochromatographic assay (ICA) based on improved up-conversion nanoparticles (IUCNPs) was developed for rapidly detecting aflatoxin B1 (AFB1) and zearalenone (ZEN). The synthesized IUCNPs doped by 30% Lu3+ showed a larger size, more regular structure, and brighter fluorescence intensity than conventional UCNPs. The limits of detection (LODs) of single-channel ICA test strips for AFB1 and ZEN detection were 0.01 and 0.1 ng/mL, respectively. After the optimization, the dual-channel ICA of AFB1 and ZEN in 10 min was conducted, resulting in low detection limits of 0.025 and 0.1 ng/mL, respectively. Moreover, the built assay was revealed to be highly specific for six other food-contaminated mycotoxins, and exhibited excellent accuracy, with corresponding R2 of 0.9931 and 0.9982 in calibration curves, respectively. Long-term storage experiments indicated that the dual-channel test strips had superior stability and precision. The LODs of AFB1 and ZEN in spiked maize were 0.025 and 0.25 µg/kg, demonstrating great sensitivity and matrix tolerance. Furthermore, the IUNCP-ICA was validated by high-performance liquid chromatography (HPLC) analyses, and a satisfactory consistency was obtained in 15 natural maize samples. Thus, the IUCNPs-ICA proposed in this work realized rapid and sensitive detection of AFB1 and ZEN, providing broad application potential in on-site screening for multiple mycotoxins in agricultural products.

Ultrafast dynamic machine vision with spatiotemporal photonic computing.

Ultrafast dynamic machine vision in the optical domain can provide unprecedented perspectives for high-performance computing. However, owing to the limited degrees of freedom, existing photonic computing approaches rely on the memory's slow read/write operations to implement dynamic processing. Here, we propose a spatiotemporal photonic computing architecture to match the highly parallel spatial computing with high-speed temporal computing and achieve a three-dimensional spatiotemporal plane. A unified training framework is devised to optimize the physical system and the network model. The photonic processing speed of the benchmark video dataset is increased by 40-fold on a space-multiplexed system with 35-fold fewer parameters. A wavelength-multiplexed system realizes all-optical nonlinear computing of dynamic light field with a frame time of 3.57 nanoseconds. The proposed architecture paves the way for ultrafast advanced machine vision free from the limits of memory wall and will find applications in unmanned systems, autonomous driving, ultrafast science, etc.

Target-activated T7 transcription circuit-mediated multiple cycling signal amplification for monitoring of flap endonuclease 1 activity in cancer cells.

The structure-specific endonuclease flap endonuclease 1 (FEN1) is an essential functional protein in DNA replication and genome stability, and it has been identified as a promising biomarker and drug target for multiple cancers. Herein, we develop a target-activated T7 transcription circuit-mediated multiple cycling signal amplification platform for monitoring FEN1 activity in cancer cells. In the presence of FEN1, the flapped dumbbell probe is cleaved to generate a free 5' flap single-stranded DNA (ssDNA) with the 3'-OH terminus. The ssDNA can hybridize with the T7 promoter-bearing template probe to trigger the extension with the aid of Klenow fragment (KF) DNA polymerase. Upon the addition of T7 RNA polymerase, an efficient T7 transcription amplification reaction is initiated to produce abundant single-stranded RNAs (ssRNAs). The ssRNA can hybridize with a molecular beacon to form an RNA/DNA heteroduplex that can be selectively digested by DSN to generate an enhanced fluorescence signal. This method exhibits good specificity and high sensitivity with a limit of detection (LOD) of 1.75 × 10-6 U µL-1. Moreover, it can be applied for the screening of FEN1 inhibitors and the monitoring of FEN1 activity in human cells, holding great potential in drug discovery and clinical diagnosis.

Characteristics of photosynthesis and vertical canopy architecture of citrus trees under two labor-saving cultivation modes using unmanned aerial vehicle (UAV)-based LiDAR data in citrus orchards.

Analyzing and comparing the effects of labor-saving cultivation modes on photosynthesis, as well as studying their vertical canopy architecture, can improve the tree structure of high-quality and high-yield citrus and selection of labor-saving cultivation modes. The photosynthesis of 1080 leaves of two labor-saving cultivation modes (wide-row and narrow-plant mode and fenced mode) comparing with the traditional mode were measured, and nitrogen content of all leaves and photosynthetic nitrogen use efficiency (PNUE) were determined. Unmanned aerial vehicle (UAV)-based light detection and ranging (LiDAR) data were used to assess the vertical architecture of three citrus cultivation modes. Results showed that for the wide-row and narrow-plant and traditional modes leaf photosynthetic CO2 assimilation rate, stomatal conductance, and transpiration rate of the upper layer were significantly higher than those of the middle layer, and values of the middle layer were markedly higher than those of the lower layer. In the fenced mode, a significant difference in photosynthetic factors between the upper and middle layers was not observed. A vertical canopy distribution had a more significant effect on PNUE in the traditional mode. Leaves in the fenced mode had distinct photosynthetic advantages and higher PNUE. UAV-based LiDAR data effectively revealed the differences in the vertical canopy architecture of citrus trees by enabling calculating the density and height percentile of the LiDAR point cloud. The point cloud densities of three cultivation modes were significantly different for all LiDAR density slices, especially at higher canopy heights. The labor-saving modes, particularly the fenced mode, had significantly higher height percentile data.