A Mendelian randomization investigation of the causal association between the gut microbiota and sleep disorders.

Background: Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders. Methods: Data on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota. Results: Inverse variance weighting (IVW) revealed a negative correlation between Coprobacter and sleep disorders (OR = 0.797, 95% CI = 0.66-0.96, and p = 0.016), a positive correlation between Lachnospiraceae and sleep disorders (OR = 1.429, 95% CI = 1.03-1.98, and p = 0.032), a negative association between Oscillospira and sleep disorders (OR = 0.745, 95% CI = 0.56-0.98, and p = 0.038), and a negative association between Peptococcus and sleep disorders (OR = 0.858, 95% CI = 0.74-0.99, p = 0.039). Conclusion: A significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, Lachnospiraceae, was observed to increase the risk of sleep disorders, while three genera, namely, Coprobacter, Oscillospira, and Peptococcus, could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.

Genomic basis of the distinct biosynthesis of ß-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species.

Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that ß-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for ß-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different ß-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding ß-glucogallin and HT biosynthesis in closely related oak species.

TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception.

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.

Kinetic study of electron transfer process in methyl orange decolorization by shewanella in MFCs with covalent organic frameworks modified anode.

As a new electrode material for electrochemical systems, covalent organic framework (COF) materials have been gradually applied to bioelectrochemical systems. In our previous study, the COFBTA-DPPD-rGO composite was synthesized via Schiff-base coupling between benzene-1,3,5-tricarbaldehyde (BTA) and 3,8-diamino-6-phenylphenanthridine (DPPD) on reduced graphene oxide (rGO) at room temperature. Here, COFBTA-DPPD-rGO modified MFC anode was used to assist microorganisms to decolorize methyl orange (MO), and the properties of MFCs were studied. The results showed that compared to the unmodified electrode MFC (28 mA m-2, 4.20 mW m-2) the current density and maximum power density of the anode MFC modified by COFBTA-DPPD-rGO (134.5 mA m-2, 21.78 mW m-2) were increased by 380.3% and 423.6%, respectively. The transferred electron number n and charge transfer coefficient α of the modified COFBTA-DPPD-rGO anode (4 and 0.43) compared to the unmodified electrode (2.4 and 0.38) were increased by 67% and 13%, respectively. The decolorization ratio of MO could reach 90.3% at 10 h. Compared with the unmodified electrode MFC (53.0%), the decolorization ratio and kinetic constant of decolorization process were enhanced by 26% and 372%, respectively. Therefore, COFBTA-DPPD-rGO could be a new choice for applying to the MFCs.

Transcription factors BZR2/MYC2 modulate brassinosteroid and jasmonic acid crosstalk during pear dormancy.

Bud dormancy is an important physiological process during winter. Its release requires a certain period of chilling. In pear (Pyrus pyrifolia), the abscisic acid (ABA)-induced expression of DORMANCY-ASSOCIATED MADS-box (DAM) genes represses bud break, whereas exogenous gibberellin (GA) promotes dormancy release. However, with the exception of ABA and GA, the regulatory effects of phytohormones on dormancy remain largely uncharacterized. In this study, we confirmed brassinosteroids (BRs) and jasmonic acid (JA) contribute to pear bud dormancy release. If chilling accumulation is insufficient, both 24-epibrassinolide (EBR) and methyl jasmonic acid (MeJA) can promote pear bud break, implying that they positively regulate dormancy release. BRASSINAZOLE RESISTANT 2 (BZR2), which is a BR-responsive transcription factor, inhibited PpyDAM3 expression and accelerated pear bud break. The transient overexpression of PpyBZR2 increased endogenous GA, JA, and JA-Ile levels. In addition, the direct interaction between PpyBZR2 and MYELOCYTOMATOSIS 2 (PpyMYC2) enhanced the PpyMYC2-mediated activation of Gibberellin 20-oxidase genes PpyGA20OX1L1 and PpyGA20OX2L2 transcription, thereby increasing GA3 contents and accelerating pear bud dormancy release. Interestingly, treatment with 5 µm MeJA increased the bud break rate, while also enhancing PpyMYC2-activated PpyGA20OX expression and increasing GA3,4 contents. The 100 µm MeJA treatment decreased the PpyMYC2-mediated activation of the PpyGA20OX1L1 and PpyGA20OX2L2 promoters and suppressed the inhibitory effect of PpyBZR2 on PpyDAM3 transcription, ultimately inhibiting pear bud break. In summary, our data provide insights into the crosstalk between the BR and JA signaling pathways that regulate the BZR2/MYC2-mediated pathway in the pear dormancy release process.

Surface lattice resonances enhanced directional amplified spontaneous emission on plasmonic honeycomb nanocone array.

Plasmonic arrays have emerged as a promising platform for investigating light-matter interactions enhanced by surface lattice resonance (SLR) at the nanoscale, which exhibit superior properties in localized field enhancement, narrow linewidth, and effective radiation loss suppression. In this study, an Al nanocone array in a honeycomb arrangement served as an optical cavity with a tip effect to realize the directional and polarized amplified spontaneous emission (ASE) of R6G. Based on the optical feedback between the degenerated SLR mode of high local density of states (LDOS) and the emission of gain media, 140-fold enhanced ASE was observed at an emission angle of 25° under TM polarization when the pump power density exceeded the threshold of 197.8 W cm-2. Moreover, polarization-resolved iso-frequency images indicated that a specific polarization dependence of ASE was modulated by the SLR mode. This study clarifies the interaction between the gain media and plasmonic system, which is beneficial for the generation of nanolasing with directional emission and lays a foundation for the plasmonic device.

Research Note: Spermatozoa proteins identification in domesticated pigeons by proteomic analysis.

Proteins are considered major effectors of sperm function. However, the proteins expressed in pigeon sperm have not been explored. Here, we collected semen from meat and racing pigeons using the electroejaculation method and identified proteins in pigeon sperm using the proteomics approach. A total of 1,641 proteins were identified in the sperm of domesticated pigeons. Of which, 1,541 proteins were reliably quantified, and gene ontology (GO) and associated bioinformatics analyses indicated that annotated proteins were linked to the oxidation-reduction process, integral component membrane, and protein binding, etc. Among quantified proteins, 1,515 and 1,507 proteins were respectively presented in White King pigeons and racing pigeons, and 1,481 proteins were shared between these 2 types of pigeons, including axonemal dynein, solute carrier, cilia- and flagella-associated protein, outer dense fiber protein, etc. Proteins in our constructed protein-protein interaction (PPI) network are involved in oxidative phosphorylation, sperm axoneme assembly, cilium-dependent cell motility, axonemal dynein complex assembly, flagellated sperm motility, etc. In conclusion, this study characterized the sperm proteome of pigeons and provided a foundation for the subsequent research screening markers for fertility evaluation of pigeons.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Simple and sensitive detection of miRNA-122 based on a micro-biosensor through square wave voltammetry.

The simple and sensitive detection of miRNA-122 in blood is crucially important for early hepatocellular carcinoma (HCC) diagnosis. In this work, a platinum microelectrode (PtµE) was prepared and electrodeposited with molybdenum disulfide (MoS2) and gold nanoparticles (AuNP), respectively, and denoted as PtµE/MoS2/Au. The prepared PtµE/MoS2/Au was used as the microsensor for the detection of miRNA-122 combined with the probe DNA as a biorecognition element which is the complementary strand of miRNA-122. The PtµE/MoS2/Au conjugated with the probe DNA modified with sulfydryl units was used as the micro-biosensor for the detection of miRNA-122. The square wave voltammetry was performed for the quantitative detection of miRNA-122 using [Fe(CN)6]4-/3- as a mediator. Under the optimized conditions, the PtµE/MoS2/Au micro-biosensor shows a linear detection toward miRNA-122 ranging from 10-11 to 10-8 M (S = 6.9 nA dec-1, R2 = 0.9997), and the detection limit is 1.6 × 10-12 M (3σ/b). The PtµE/MoS2/Au micro-biosensor demonstrates good selectivity against other types of proteins and small molecules, and has good reproducibility. Moreover, the PtµE/MoS2/Au micro-biosensor was successfully applied for the measurement of miRNA-122 in real blood samples. Herein, the proposed detection assay could be a potential tool in HCC clinical diagnostics with high sensitivity.

The ethylene-responsive transcription factor PpERF9 represses PpRAP2.4 and PpMYB114 via histone deacetylation to inhibit anthocyanin biosynthesis in pear.

Ethylene induces anthocyanin biosynthesis in most fruits, including apple (Malus domestica) and plum (Prunus spp.). By contrast, ethylene inhibits anthocyanin biosynthesis in pear (Pyrus spp.), but the underlying molecular mechanism remains unclear. In this study, we identified and characterized an ethylene-induced ETHYLENE RESPONSE FACTOR (ERF) transcription factor, PpETHYLENE RESPONSE FACTOR9 (PpERF9), which functions as a transcriptional repressor. Our analyses indicated PpERF9 can directly inhibit expression of the MYB transcription factor gene PpMYB114 by binding to its promoter. Additionally, PpERF9 inhibits the expression of the transcription factor gene PpRELATED TO APETALA2.4 (PpRAP2.4), which activates PpMYB114 expression, by binding to its promoter, thus forming a PpERF9-PpRAP2.4-PpMYB114 regulatory circuit. Furthermore, PpERF9 interacts with the co-repressor PpTOPLESS1 (PpTPL1) via EAR motifs to form a complex that removes the acetyl group on histone H3 and maintains low levels of acetylated H3 in the PpMYB114 and PpRAP2.4 promoter regions. The resulting suppressed expression of these 2 genes leads to decreased anthocyanin biosynthesis in pear. Collectively, these results indicate that ethylene inhibits anthocyanin biosynthesis by a mechanism that involves PpERF9-PpTPL1 complex-mediated histone deacetylation of PpMYB114 and PpRAP2.4. The data presented herein will be useful for clarifying the relationship between chromatin status and hormone signaling, with implications for plant biology research.

PpyABF3 recruits the COMPASS-like complex to regulate bud dormancy maintenance via integrating ABA signaling and GA catabolism.

Bud dormancy is essential for perennial trees that survive the cold winters and to flower on time in the following spring. Histone modifications have been reported to be involved in the control of the dormancy cycle and DAM/SVPs are considered targets. However, how the histone modification marks are added to the specific gene loci during bud dormancy cycle is still unknown. Using yeast-two hybrid library screening and co-immunoprecipitation assays, we found that PpyABF3, a key protein regulating bud dormancy, recruits Complex of Proteins Associated with Set1-like complex via interacting with PpyWDR5a, which increases the H3K4me3 deposition at DAM4 locus. Chromatin immunoprecipitation-quantitative polymerase chain reaction showed that PpyGA2OX1 was downstream gene of PpyABF3 and it was also activated by H3K4me3 deposition. Silencing of GA2OX1 in pear calli and pear buds resulted in a similar phenotype with silencing of ABF3. Furthermore, overexpression of PpyWDR5a increased H3K4me3 levels at DAM4 and GA2OX1 loci and inhibited the growth of pear calli, whereas silencing of PpyWDR5a in pear buds resulted in a higher bud-break percentage. Our findings provide new insights into how H3K4me3 marks are added to dormancy-related genes in perennial woody plants and reveal a novel mechanism by which ABF3 integrates abscisic acid signaling and gibberellic acid catabolism during bud dormancy maintenance.

Early defoliation induces auxin redistribution, promoting paradormancy release in pear buds.

Paradormancy of fruit trees occurs in summer and autumn when signals from adjacent organs stimulate buds to develop slowly. This stage has received less attention that the other stages of dormancy, and the underlying mechanism remains uncharacterized. Early defoliation in late summer and early autumn is usually followed by out-of-season blooming in pear (Pyrus spp.), which substantially decreases the number of buds the following spring and negatively affects fruit production. This early bud flush is an example of paradormancy release. Here, we determined that flower bud auxin content is stable after defoliation; however, polar distribution of the pear (Pyrus pyrifolia) PIN-FORMED auxin efflux carrier 1b (PpyPIN1b) implied that auxin tends to be exported from buds. Transcriptome analysis of floral buds after artificial defoliation revealed changes in auxin metabolism, transport, and signal transduction pathways. Exogenous application of a high concentration of the auxin analog 1-naphthaleneacetic acid (300 mg/L) suppressed PpyPIN1b expression and its protein accumulation in the cell membrane, likely leading to decreased auxin efflux from buds, which hindered flower bud sprouting. Furthermore, carbohydrates and additional hormones also influenced out-of-season flowering. Our results indicate that defoliation-induced auxin efflux from buds accelerates bud paradormancy release. This differs from release of apical-dominance-related lateral bud paradormancy after the apex is removed. Our findings and proposed model further elucidate the mechanism underlying paradormancy and will help researchers to develop methods for inhibiting early defoliation-induced out-of-season bud sprouting.

PpZAT5 suppresses the expression of a B-box gene PpBBX18 to inhibit anthocyanin biosynthesis in the fruit peel of red pear.

BBX (B-box) proteins play a vital role in light-induced anthocyanin biosynthesis. PpBBX18 was an indispensable regulator for the induction of anthocyanin biosynthesis in the peel of red pear fruit (Pyrus pyrifolia Nakai.). However, the upstream regulation of BBX genes has not been well characterized. In this study, PpZAT5, a cysteine2/histidine2-type transcription factor, was discovered as the upstream negative regulator of PpBBX18. The results showed that PpZAT5 functions as a transcriptional repressor and directly binds to the CAAT motif of PpBBX18 and inhibits its expression. PpZAT5 expression was inhibited by light, which is converse to the expression pattern of anthocyanin-related structural genes. In addition, less anthocyanin accumulated in the PpZAT5-overexpressing pear calli than in the wild-type pear calli; on the contrary, more anthocyanin accumulated in PpZAT5-RNAi pear calli. Moreover, the crucial genes involved in light-induced anthocyanin biosynthesis were markedly down-regulated in the transcriptome of PpZAT5 overexpression pear calli compared to wild-type. In conclusion, our study indicates that PpBBX18 is negatively regulated by a C2H2-type transcriptional repressor, PpZAT5, which reduces anthocyanin content in pear. The present results demonstrate an upstream molecular mechanism of PpBBX18 and provide insights into light-induced anthocyanin biosynthesis.

Improving glutathione production by engineered Pichia pastoris: strain construction and optimal precursor feeding.

Glutathione (GSH) is a metabolite that plays an important role in the fields of pharmacy, food, and cosmetics. Thus, it is necessary to increase its production to meet the demands. In this study, ScGSH1, ScGSH2, and StGshF were heterologously expressed in Pichia pastoris GS115 to realize the dual-path synthesis of GSH in yeast. To explore the effects of ATP metabolism on the synthesis of GSH, enzymes (ScADK1, PpADK1, VsVHB) of the ATP-related metabolic pathway and the energy co-substrate sodium citrate were taken into account. We found that both ScADK1 and sodium citrate had a positive influence on the synthesis of GSH. Then, a fermentation experiment in Erlenmeyer flasks was performed using the G3-SF strain (containing ScGSH1, ScGSH2, StGshF, and ScADK1), with the highest GSH titer and yield of 999.33 ± 47.26 mg/L and 91.53 ± 4.70 mg/g, respectively. Finally, the fermentation was scaled up in a 5-L fermentor, and the highest titer and yield were improved to 5680 mg/L and 45.13 mg/g, respectively, by optimizing the addition conditions of amino acids (40 mM added after 40 h). Our work provides an alternative strategy by combining dual-path synthesis with energy metabolism regulation and precursor feeding to improve GSH production. Key Points • ScGSH1, ScGSH2, and StGshF were overexpressed to achieve dual-path synthesis of GSH in yeast. • ScADK1 was overexpressed, and sodium citrate was added to increase the energy supply for GSH synthesis. • The addition conditions of amino acids were optimized to realize the efficient synthesis of GSH.

Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis.

Growing evidence suggests that the bidirectional interactions between cancer cells and their surrounding environment, namely the tumor microenvironment (TME), contribute to cancer progression, metastasis, and resistance to treatment. Intense investigation of the Hippo pathway, which controls multiple central cellular functions in tumorigenesis, was focused on cancer cells. However, the role of the Hippo pathway in modulating tumor-stromal interactions in triple-negative breast cancer remains largely unknown. Therefore, this study focused on revealing the effects of Hippo-YAP/TAZ signaling on the immune microenvironment. Our findings reveal that the activity of the Hippo pathway is associated with worse disease outcomes in TNBC and could increase TAM infiltration through the TAZ/IL-34 axis, leading to an immunosuppressive microenvironment and impairing the treatment efficacy of anti-PD-L1. Thus, the TAZ/IL-34 axis may serve as a novel target for TNBC patients.

Light-responsive transcription factor PpWRKY44 induces anthocyanin accumulation by regulating PpMYB10 expression in pear.

Anthocyanins are a valuable source of antioxidants in the human diet and contribute to fruit coloration. In red-skinned pears, anthocyanin biosynthesis can be induced by light, in which the MYB-bHLH-WDR complex plays a critically important role in transcriptional regulation. However, knowledge of WRKY-mediated transcriptional regulation of light-induced anthocyanin biosynthesis is scarce in red pears. This work identified and functionally characterized a light-inducing WRKY transcription factor, PpWRKY44, in pear. Functional analysis based on overexpressed pear calli showed that PpWRKY44 promoted anthocyanin accumulation. Also, transiently overexpressed PpWRKY44 in pear leaves and fruit peels significantly enhanced the accumulation of anthocyanin, whereas silencing PpWRKY44 in pear fruit peels impaired induction of the accumulation of anthocyanin by light. By chromatin immunoprecipitation and electrophoretic mobility shift assay coupled to a quantitative polymerase chain reaction, we found that PpWRKY44 bound in vivo and in vitro to the PpMYB10 promoter, revealing it as a direct downstream target gene. Moreover, PpWRKY44 was activated by PpBBX18, a light signal transduction pathway component. Our results explained the mechanism mediating the impacts of PpWRKY44 on the transcriptional regulation of anthocyanin accumulation, with potential implications for fine-tuning the fruit peel coloration triggered by light in red pears.

Dlg1 Knockout Inhibits Microglial Activation and Alleviates Lipopolysaccharide-Induced Depression-Like Behavior in Mice.

Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K+ channels, which are reported to regulate the activation of microglia. However, little is known about the role of Dlg1 in microglia and the maintenance of central nervous system homeostasis. In this study, we found that Dlg1 knockdown suppressed lipopolysaccharide (LPS)-induced inflammation by down-regulating the activation of nuclear factor-κB signaling and the mitogen-activated protein kinase pathway in microglia. Moreover, using an inducible Dlg1 microglia-specific knockout (Dlg1flox/flox; CX3CR1CreER) mouse line, we found that microglial Dlg1 knockout reduced the activation of microglia and alleviated the LPS-induced depression-like behavior. In summary, our results demonstrated that Dlg1 plays a critical role in microglial activation and thus provides a potential therapeutic target for the clinical treatment of depression.

Simplified Near-Degenerate Four-Wave-Mixing Microscopy.

Four-wave-mixing microscopy is widely researched in both biology and medicine. In this paper, we present a simplified near-degenerate four-wave-mixing microscopy (SNDFWM). An ultra-steep long-pass filter is utilized to produce an ultra-steep edge on the spectrum of a femtosecond pulse, and a super-sensitive four-wave-mixing (FWM) signal can be generated via an ultra-steep short-pass filter. Compared with the current state-of-the-art FWM microscopy, this SNDFWM microscopy has the advantages of simpler experimental apparatus, lower cost, and easier operation. We demonstrate that this SNDFWM microscopy has high sensitivity and high spatial resolution in both nanowires and biological tissues. We also show that the SNDFWM microscopy can achieve an ultra-sensitive detection based on the electron-resonance effect. This method might find an important application in tracking of nano drugs in vivo.

High-quality genome assembly of 'Cuiguan' pear (Pyrus pyrifolia) as a reference genome for identifying regulatory genes and epigenetic modifications responsible for bud dormancy.

Dormancy-associated MADS-box (DAM) genes serve as crucial regulators of the endodormancy cycle in rosaceous plants. Although pear DAM genes have been identified previously, the lack of a high-quality reference genome and techniques to study gene function have prevented accurate genome-wide analysis and functional verification of such genes. Additionally, the contribution of other genes to the regulation of endodormancy release remains poorly understood. In this study, a high-quality genome assembly for 'Cuiguan' pear (Pyrus pyrifolia), which is a leading cultivar with a low chilling requirement cultivated in China, was constructed using PacBio and Hi-C technologies. Using this genome sequence, we revealed that pear DAM genes were tandemly clustered on Chr8 and Chr15 and were differentially expressed in the buds between 'Cuiguan' and the high-chilling-requirement cultivar 'Suli' during the dormancy cycle. Using a virus-induced gene silencing system, we determined the repressive effects of DAM genes on bud break. Several novel genes potentially involved in the regulation of endodormancy release were identified by RNA sequencing and H3K4me3 chromatin immunoprecipitation sequencing analyses of 'Suli' buds during artificial chilling using the new reference genome. Our findings enrich the knowledge of the regulatory mechanism underlying endodormancy release and chilling requirements and provide a foundation for the practical regulation of dormancy release in fruit trees as an adaptation to climate change.

Metal Phenolic Network-Integrated Multistage Nanosystem for Enhanced Drug Delivery to Solid Tumors.

Metal-phenolic networks (MPNs) are an emerging class of supramolecular surface modifiers with potential use in various fields including drug delivery. Here, the development of a unique MPN-integrated core-satellite nanosystem (CS-NS) is reported. The "core" component of CS-NS comprises a liposome loaded with EDTA (a metal ion chelator) in the aqueous core and DiR (a near-infrared photothermal transducer) in the bilayer. The "satellite" component comprises mesoporous silica nanoparticles (MSNs) encapsulating doxorubicin and is coated with a Cu2+ -tannic acid MPN. Liposomes and MSNs self-assemble into the CS-NS through adhesion mediated by the MPN. When irradiated with an 808 nm laser, CS-NS liberated the entrapped EDTA, leading to Cu2+ chelation and subsequent disassembly of the core-satellite nanostructure. Photo-conversion from the large assembly to the small constituent particles proceeded within 5 min. Light-triggered CS-NS disassembly enhanced the carrier and cargo penetration and accumulation in tumor spheroids in vitro and in orthotopic murine mammary tumors in vivo. CS-NS is long circulating in the blood and conferred improved survival outcomes to tumor-bearing mice treated with light, compared to controls. These results demonstrate an MPN-integrated multistage nanosystem for improved solid tumor treatment.