Benzo(a)anthracene Targeting SLC1A5 to Synergistically Enhance PAH Mixture Toxicity.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) as mutagenic and carcinogenic pollutants in the environment often occurs in the form of mixtures. Although the mixture effects of PAHs have been previously recognized, the toxicological mechanisms to explain them still remain quite unclear. This study combined metabolomics and chemical proteomics methods to comprehensively understand the mixture effects of a PAH mixture including benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), and chrysene (CHR). Among them, BaA has shown a strong synergistic effect with other PAHs. Interestingly, BaA alone is not a potent oxidative stress inducer in liver cells but dose-dependently amplifies oxidative damage caused by the PAH mixture. Global metabolomics analysis results revealed damage to the antioxidant glutathione synthesis, which was caused by the glutamine depletion caused by BaA in the mixture. Subsequently, the label-free chemical proteomics and cellular thermal shift analysis (CETSA) demonstrated that the PAH mixture altered the thermal shift of glutamine transporter SLC1A5. Furthermore, Western blotting and the isothermal titration calorimetry (ITC) interaction measurements showed nanomolar KD values between BaA and SLC1A5. Overall, this study showed that BaA synergistically contributed to PAH mixture induced oxidative damage by targeting SLC1A5 to inhibit glutamate transport into cells, resulting in the inhibition of glutathione synthesis.

Resistance of the CRISPR-Cas13a Gene-Editing System to Potato Spindle Tuber Viroid Infection in Tomato and Nicotiana benthamiana.

Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into Nicotiana benthamiana through transgenic methods, using CRISPR RNAs (crRNAs) targeting the conserved regions of both sense and antisense genomes of potato spindle tuber viroid (PSTVd). In tomato plants, the expression of CRISPR-Cas13a and crRNAs substantially reduced PSTVd accumulation and alleviated disease symptoms. In transgenic N. benthamiana plants, the PSTVd levels were lower as compared to wild-type plants. Several effective crRNAs targeting the PSTVd genomic RNA were also identified. These results demonstrate that the CRISPR-Cas13a system can effectively target and combat viroid RNAs, despite their compact structures.

Integrated Thermal Proteome Profiling and Affinity Ultrafiltration Mass Spectrometry (iTPAUMS): A Novel Paradigm for Elucidating the Mechanism of Action of Natural Products.

Natural products (NPs) are foundational to drug discovery, offering a rich repertoire of molecular diversity with multifaceted modes of action against a broad array of targets. Despite their potential, deconvoluting the intricate mechanism of action (MoA) of NPs, characterized by their multicomponent, multitarget, and multilevel interactions, remains a formidable challenge. Here, we introduce an innovative pipeline called integrated thermal proteome profiling and affinity ultrafiltration mass spectrometry (iTPAUMS). This approach combines the high-throughput capacity of thermal proteome profiling (TPP) with the specificity of affinity ultrafiltration mass spectrometry (AUMS), creating a powerful toolkit for elucidating complex MoAs of NPs. Significantly, our investigation represents a pioneering application of TPP to delineate the target group of NPs mixtures and overcome the long-standing obstacle of mapping specific component-target interactions through AUMS. Our findings demonstrate the utility of iTPAUMS in constructing a comprehensive component-target atlas, providing a robust analytical foundation for unraveling the intricate pharmacological landscapes of NPs and advancing drug discovery.

Electrochemical stability of biodegradable Zn-Cu alloys through machine-learning accelerated high-throughput discovery.

Zn-Cu alloys have attracted great attention as biodegradable alloys owing to their excellent mechanical properties and biocompatibility, with corrosion characteristics being crucial for their suitability for biomedical applications. However, the unresolved identification of intermetallic compounds in Zn-Cu alloys affecting corrosion and the complexity of the application environment hamper the understanding of their electrochemical behavior. Utilizing high-throughput first-principles calculations and machine-learning accelerated evolutionary algorithms for screening the most stable compounds in Zn-Cu systems, a dataset encompassing the formation energy of 2033 compounds is generated. It reveals that most of the experimentally reported Zn-Cu compounds can be replicated, especially the structure of R32 CuZn5 is first discovered which possesses the lowest formation energy of -0.050 eV per atom. Furthermore, the simulated X-ray diffraction pattern matches perfectly with the experimental ones. By formulating 342 potential electrochemical reactions based on the binary compounds, the Pourbaix diagrams for Zn-Cu alloys are constructed to clarify the fundamental competition between different phases and ions. The calculated equilibrium potential of CuZn5 is higher than that of Zn through the forward reaction Zn + CuZn5 ⇌ CuZn5 + Zn2+ + 2e-, resulting in microcell formation owing to the stronger charge density localization in Zn compared to CuZn5. The presence of chlorine accelerates the corrosion of Zn through the reaction Zn + CuZn5 + 6Cl- + 6H2O ⇌ Cu + 6ZnOHCl + 6H+ + 12e-, where the formation of ZnOHCl disrupts the ZnO passive film and expands the corrosion pH range from 9.2 to 8.8. Our findings reveal an accurate quantitative corrosion mechanism for Zn-Cu alloys, providing an effective pathway to investigate the corrosion resistance of biodegradable alloys.

Field measurements of turbulent mixing south of the Lombok Strait, Indonesia.

The Indonesian seas, with their complex passages and vigorous mixing, constitute the only route and are critical in regulating Pacific-Indian Ocean interchange, air-sea interaction, and global climate events. Previous research employing remote sensing and numerical simulations strongly suggested that this mixing is tidally driven and localized in narrow channels and straits, with only a few direct observations to validate it. The current study offers the first comprehensive temporal microstructure observations in the south of Lombok Strait with a radius of 0.05° and centered on 115.54oE and 9.02oS. Fifteen days of tidal mixing observations measured potential temperature and density, salinity, and turbulent energy dissipation rate. The results revealed significant mixing and verified the remotely sensed technique. The south Lombok temporal and depth averaged of the turbulent kinetic energy dissipation rate, and the diapycnal diffusivity from 20 to 250 m are ε  = 4.15 ± 15.9) × 10-6 W kg-1 and K ρ = (1.44 ± 10.7) × 10-2 m2s-1, respectively. This K ρ is up to 104 times larger than the Banda Sea [ K ρ  = (9.2 ± 0.55) × 10-6 m2s-1] (Alford et al. Geophys Res Lett 26:2741-2744, 1999) or the "open ocean" K ρ = 0.03 × 10-4 m2s-1 within 2° of the equator to (0.4-0.5) × 10-4 m2s-1 at 50°-70° (Kunze et al. J Phys Oceanogr 36:1553-1576, 2006). Therefore, nonlinear interactions between internal tides, tidally induced mixing, and ITF plays a critical role regulating water mass transformation and have strong implications to longer-term variations and change of Pacific-Indian Ocean water circulation and climate. Supplementary Information: The online version contains supplementary material available at 10.1186/s40562-024-00349-3.

Van der Waals mid-wavelength infrared detector linear array for room temperature passive imaging.

Passive imaging for mid-wave infrared (MWIR) is resistant to atmospheric pollutants, guaranteeing image clarity and accuracy. Arrayed photodetectors can simultaneously perform radiation sensing to improve efficiency. Room temperature van der Waals (vdWs) photodetectors without lattice matching have evolved rapidly with optimized stacking methods, primarily for single-pixel devices. The urgent need to implement arrayed devices aligns with practical demands. Here, we present an 8 by 1 black phosphorus/molybdenum sulfide (BP/MoS2) vdWs photodetector linear array with a fill-factor of ~77%, fabricated using a temperature-assisted sloping transfer method. The flat interface and uniform thickness facilitate carrier transport and minimize pixel nonuniformities, showing an average peak detectivity (D*) of 2.34 × 109 cm·Hz1/2·W-1 in the mid-wave infrared region. Compared to a single pixel, push-broom scanning passive imaging is eight times more efficient and further enhanced through mean filtering and fast Fourier transform filtering for strip noise correction. Our study offers guidance on vdWs arrayed devices for engineering applications.

GSK3: A potential target and pending issues for treatment of Alzheimer's disease.

Glycogen synthase kinase-3 (GSK3), consisting of GSK3α and GSK3ß subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder with diverse pathogenesis and notable cognitive impairments, characterized by Aß aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, extensively analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function. It directly promotes tau phosphorylation, regulates amyloid precursor protein (APP) cleavage, leading to Aß formation, and directly or indirectly triggers neuroinflammation and oxidative damage. We also summarize preclinical research highlighting the inhibition of GSK3 activity as a primary therapeutic approach for AD. Finally, pending issues like the lack of highly specific and affinity-driven GSK3 inhibitors, are raised and expected to be addressed in future research. In conclusion, GSK3 represents a target in AD treatment, filled with hope, challenges, opportunities, and obstacles.

Association of serum resolvin D1 with the risk of major adverse cardiovascular events in hemodialysis patients.

PURPOSE: Resolvin D1 (RvD1) inhibits inflammation, reduces oxidative stress, and forecasts the risk of cardiovascular events, but relevant evidence in hemodialysis patients is lacking. This study intended to investigate the predictive value of RvD1 for major adverse cardiovascular events (MACE) risk in hemodialysis patients. METHODS: Totally, 252 patients who underwent hemodialysis were included. Serum RvD1 was measured by enzyme-linked immunosorbent assay. Patients were followed up with a median of 12.1 months. MACE was recorded during the follow-up period. RESULTS: RvD1 was inversely correlated with diabetes history (P = 0.002), cardiac troponin T (TnT) (P = 0.029), and high sensitivity C-reactive protein (hsCRP) (P < 0.001) in hemodialysis patients. 25 hemodialysis patients experienced MACE. RvD1 was reduced in hemodialysis patients with MACE versus those without MACE (P = 0.004). RvD1 exhibited a certain value in forecasting MACE risk, with an area under curve (AUC) of 0.675 [95% confidence interval CI: 0.565-0.786]. Increased RvD1 cut by median (P = 0.043) and cut by quartile (P = 0.042) were related to decreased accumulating MACE in hemodialysis patients. Moreover, RvD1 independently predicted declined MACE risk [odds ratio (OR) = 0.644, P = 0.045], but age (OR = 1.048, P = 0.039) and TnT (OR = 1.006, P = 0.005) independently predicted ascended MACE risk in hemodialysis patients. The combination of these independent factors displayed a good value for estimating MACE risk in hemodialysis patients with an AUC of 0.744 (95% CI: 0.640-0.849). CONCLUSION: Serum RvD1 is inversely correlated with diabetes history, TnT, and hsCRP in hemodialysis patients. More importantly, it could serve as a potential marker to predict MACE risk in these patients.

Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation.

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy.

HPK1, a well-known negative regulator of T cell receptors, can cause T cell dysfunction when abnormally activated. In this study, a PROTAC C3 was designed and synthesized by optimizing the physicochemical properties of the warhead, linker, and CRBN ligand. C3 demonstrated significant HPK1 degradation with a DC50 of 21.26 nM, excellent oral absorption with a Cmax of 10,899.92 ng/mL, and a bioavailability (F %) of 81.7%. C3 also showed degradation selectivity and potent immune activation effects. Proteomic and WB analyses revealed that immune-activating effect of C3 is attributed to the inhibition of SLP76 and NF-κB signaling pathways, as well as the enhancement of MAPK signaling pathway transduction. In vivo efficacy study demonstrated that oral administration of C3 in combination with anti-PDL1 antibody significantly inhibited tumor growth (tumor growth inhibition = 65.58%). These findings suggest that C3, a novel HPK1 PROTAC, holds promise as a therapeutic agent for tumor immunotherapy.

Integrated metabolomics and proteomics analyses to reveal anticancer mechanism of hemp oil extract in colorectal cancer.

Cannabis sativa L., with a rich history in Chinese folk medicine, includes hemp strains that offer substantial economic and medical benefits due to their non-addictive properties. Hemp has demonstrated various pharmaceutical activities, including anti-inflammatory, antioxidant, and anti-tumor effects. This study explores the potential of hemp oil extract (HOE) in treating colorectal cancer (CRC). Despite its promise, the specific anticancer mechanisms of HOE have not been well understood. To elucidate these mechanisms, we employed mass spectrometry-based metabolomics and proteomics to investigate the global effects of HOE on CRC cells. Additionally, bioinformatics approaches, including bulk RNA-seq and single-cell RNA-seq, were used to identify gene expression differences and cellular heterogeneity. The results were validated using flow cytometry, western blotting, and immunohistochemistry. Our findings reveal that HOE induces significant alterations in purine metabolism pathways, down-regulates c-MYC, and inhibits the expression of cell cycle-related proteins such as CCND1, CDK4, and CDK6, leading to cell cycle arrest in the G1 phase. This comprehensive analysis demonstrates that HOE effectively blocks the cell cycle in the G1 phase, thereby inhibiting colorectal cancer cell proliferation. These findings provide experimental evidence supporting the potential therapeutic use of hemp in medicine.

Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors.

BRD9 is a pivotal epigenetic factor involved in cancers and inflammatory diseases. Still, the limited selectivity and poor phenotypic activity of targeted agents make it an atypically undruggable target. PROTAC offers an alternative strategy for overcoming the issue. In this study, we explored diverse E3 ligase ligands for the contribution of BRD9 PROTAC degradation. Through molecular docking, binding affinity analysis, and structure-activity relationship study, we identified a highly potent PROTAC E5, with excellent BRD9 degradation (DC50 = 16 pM) and antiproliferation in MV4-11 cells (IC50 = 0.27 nM) and OCI-LY10 cells (IC50 = 1.04 nM). E5 can selectively degrade BRD9 and induce cell cycle arrest and apoptosis. Moreover, the therapeutic efficacy of E5 was confirmed in xenograft tumor models, accompanied by further RNA-seq analysis. Therefore, these results may pave the way and provide the reference for the discovery and investigation of highly effective PROTAC degraders.

Simultaneous measurement of bidirectional magnetic field and temperature with a dual-channel sensor based on the whispering gallery mode.

What we believe is a novel dual-channel whispering gallery mode (WGM) sensor for concurrently measuring bidirectional magnetic field and temperature is proposed and demonstrated. Two sensing microcavities [magnetic fluid (MF)-infiltrated capillary and polydimethylsiloxane (PDMS)-coated microbottle, respectively, referred as Channel 1 (CH1) and Channel 2 (CH2)] are integrated into a silica capillary to facilitate the dual-channel design. Resonant wavelengths corresponding to CH1 and CH2 mainly depend on the change in the magneto-induced refractive index and the change in the thermo-induced parameter (volume and refractive index) of the employed functional materials, respectively. The MF-infiltrated capillary enables bidirectional magnetic field sensing with maximum sensitivities of 46 pm/mT and -3 pm/mT, respectively. The PDMS-coated structure can realize the temperature measurement with a maximum sensitivity of 79.7 pm/°C. The current work possesses the advantage of bidirectionally magnetic tunability besides the temperature response, which is expected to be used in field such as vector magnetic fields and temperature dual-parameter sensing.

Black soldier fly (Hermetia illucens L.): A potential small mighty giant in the field of cosmeceuticals.

Background and Aims: Natural products are widely used in the pharmaceutical and cosmetics industries due to their high-value bioactive compounds, which make for "greener" and more environmentally friendly ingredients. These natural compounds are also considered a safer alternative to antibiotics, which may result in antibiotic resistance as well as unfavorable side effects. The development of cosmeceuticals, which combine the cosmetic and pharmaceutical fields to create skincare products with therapeutic value, has increased the demand for unique natural resources. The objective of this review is to discuss the biological properties of extracts derived from larvae of the black soldier fly (BSF; Hermetia illucens), the appropriate extraction methods, and the potential of this insect as a novel active ingredient in the formulation of new cosmeceutical products. This review also addresses the biological actions of compounds originating from the BSF, and the possible association between the diets of BSF larvae and their subsequent bioactive composition. Methods: A literature search was conducted using PubMed and Google Scholar to identify and evaluate the various biological properties of the BSF. Results: One such natural resource that may be useful in the cosmeceutical field is the BSF, a versatile insect with numerous potential applications due to its nutrient content and scavenging behavior. Previous research has also shown that the BSF has several biological properties, including antimicrobial, antioxidant, anti-inflammatory, and wound healing effects. Conclusion: Given the range of biological activities and metabolites possessed by the BSF, this insect may have the cosmeceutical potential to treat a number of skin pathologies.

ADAM10 Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Activating the Notch Signaling Pathway.

The occurrence of myocardial ischemia/reperfusion injury is commonly observed during cardiac surgery; however, there remains a dearth of effective therapeutic strategies to mitigate this injury. The a disintegrin and metallopeptidase domain 10 (ADAM10) is a transmembrane protein anchored on the cell membrane surface, and its precise mechanism of action in myocardial ischemia/reperfusion injury remains incompletely understood. This study aims to investigate the impact of ADAM10 on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) and elucidate the underlying mechanisms. The ADAM10 overexpression plasmid was transfected into H9c2 cells, which were subsequently treated with the Notch signaling pathway inhibitor DAPT and cultured under H/R conditions. Cell proliferation activity was assessed using the CCK-8 assay. The levels of LDH, SOD, and MDA were quantified through colorimetric analysis. The levels of ROS and the rate of apoptosis were measured using flow cytometry. The morphological changes in the nucleus of H9c2 cells were observed by employing Hoechst 33258 staining. The mRNA expression levels of ADAM10, Notch1, NICD, and Hes1 in H9c2 cells were determined using qRT-PCR. The expressions of Notch signaling pathway and apoptosis-related proteins were analyzed by Western blot. Overexpression of ADAM10 provided protection to H9c2 cells against injury induced by H/R, leading to an increase in SOD levels and alleviation of oxidative stress caused by the accumulation of ROS and the decrease of SOD activity. Meanwhile, overexpression of ADAM10 inhibited apoptosis in H9c2 cells exposed to H/R by regulating the expression of apoptosis-related proteins, such as Bax, Bcl-2 and Cleaved-caspase-3. Additionally, overexpression of ADAM10 facilitated the activation of the Notch1 signaling pathway in H9c2 cells exposed to H/R by upregulating the protein expression of Notch1, NICD, and Hes1. However, the protective effect of ADAM10 on H/R-induced H9c2 cells was partially reversed by DAPT. Our findings demonstrate that ADAM10 exerts protective effects in H/R-induced H9c2 cells by suppressing oxidative stress and apoptosis via the activation of the Notch signaling pathway.

Network pharmacology combined with affinity ultrafiltration to elucidate the potential compounds of Shaoyao Gancao Fuzi Decoction for the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao Gancao Fuzi Decoction (SGFD), has been employed for thousands of years in the treatment of rheumatoid arthritis (RA) with remarkable clinical efficacy. However, the material basis underlying the effectiveness of SGFD still remains unclear. AIM OF THE REVIEW: This study aims to elucidate the material basis of SGFD through the application of network pharmacology and biological affinity ultrafiltration. RESULTS: UPLC-Q-TOF-MS/MS was employed to characterize the components in SGFD, the identified 145 chemical components were mainly categorized into alkaloids, flavonoids, triterpenoids, and monoterpenoids according to the structures. Network pharmacology method was utilized to identify potential targets and signaling pathways of SGFD in the RA treatment, and the anti-inflammatory and anti-RA effects of SGFD were validated through in vivo and in vitro experiments. Moreover, as the significant node in the pharmacology network, TNF-α, a classical therapeutic target in RA, was subsequent employed to screen the interacting compounds in SGFD via affinity ultrafiltration screening method, 6 active molecules (i.e.,glycyrrhizic acid, paeoniflorin, formononetin, isoliquiritigenin, benzoyl mesaconitine, and glycyrrhetinic acid) were exhibited significant interactions. Finally, the significant anti-inflammatory and anti-TNF-α effects of these compounds were validated at the cellular level. CONCLUSIONS: In conclusion, this study comprehensively elucidates the pharmacodynamic material basis of SGFD, offering a practical reference model for the systematic investigation of traditional Chinese medicine formulas.

Black Arsenic Phosphorus Mid-Wave Infrared Barrier Detector with High Detectivity at Room Temperature.

The barrier structure is designed to enhance the operating temperature of the infrared detector, thereby improving the efficiency of collecting photogenerated carriers and reducing dark current generation, without suppressing the photocurrent. However, the development of barrier detectors using conventional materials is limited due to the strict requirements for lattice and band matching. In this study, a high-performance unipolar barrier detector is designed utilizing a black arsenic phosphorus/molybdenum disulfide/black phosphorus van der Waals heterojunction. The device exhibits a broad response bandwidth ranging from visible light to mid-wave infrared (520 nm to 4.6 µm), with a blackbody detectivity of 2.7 × 1010 cmHz-1/2 W-1 in the mid-wave infrared range at room temperature. Moreover, the optical absorption anisotropy of black arsenic phosphorus enables polarization resolution detection, achieving a polarization extinction ratio of 35.5 at 4.6 µm. Mid-wave infrared imaging of the device is successfully demonstrated at room temperature, highlighting the significant potential of barrier devices based on van der Waals heterojunctions in mid-wave infrared detection.

Measurement and Data Correction of Channel Sampling Timing Walk-Off of Photonic Analog-to-Digital Converter in Signal Recovery.

A two-channel, time-wavelength interleaved photonic analog-to-digital converter (PADC) system with a sampling rate of 10.4 GSa/s was established, and a concise method for measuring and data correcting the channel sampling timing walk-off of PADCs for signal recovery was proposed. The measurements show that for the two RF signals of f1 = 100 MHz and f2 = 200 MHz, the channel sampling timing walk-off was 12 sampling periods, which results in an ENOB = -0.1051 bits for the 100 MHz directly synthesized signal, while the ENOB improved up to 4.0136 bits using shift synthesis. In addition, the peak limit method (PLM) and normalization processing were introduced to reduce the impacts of signal peak jitter and power inconsistency between two channels, which further improve the ENOB of the 100 MHz signal up to 4.5668 bits. All signals were analyzed and discussed in both time and frequency domains. The 21.1 GHz signal was also collected and converted using the established two-channel PADC system with the data correction method, combining the PLM, normalization, and shift synthesis, showing that the ENOB increased from the initial -0.9181 to 4.1913 bits, which demonstrates that our method can be effectively used for signal recovery in channel-interleaved PADCs.

miR156b-targeted VvSBP8/13 functions downstream of the abscisic acid signal to regulate anthocyanins biosynthesis in grapevine fruit under drought.

Anthocyanins are the primary color components of grapevine berries and wines. In cultivation practices, a moderate water deficit can promote anthocyanin accumulation in red grape skins. Our previous study showed that abscisic acid (ABA) plays a key role in this process. Herein, we identified a microRNA, vv-miR156b, that is generated in grapevine berries in response to drought stress, along with increasing anthocyanin content and biosynthetic structural gene transcripts. In contrast, vv-miR156b short tandem target mimic (STTM) function-loss callus exhibits the opposite phenotype. Results from in vivo and in vitro experiments revealed that the ABA-signaling-regulated transcription factor VvAREB2 binds directly to the ABA-responsive element (ABRE) of the MIR156b promoter and activates miR156b expression. Furthermore, two miR156b downstream targets, VvSBP8 and VvSBP13, exhibited reduced grape anthocyanin content in their overexpressors but there was a contrary result in their CRISPR-edited lines, the decrease in anthocyanin content was rescued in miR156b and SBP8/13 double overexpressors. We further demonstrated that both VvSBP8 and VvSBP13, encoding transcriptional repressors, displayed sufficient ability to interact with VvMYC1 and VvMYBA1, thereby interfering with MYB-bHLH-WD (MBW) repeat transcriptional complex formation, resulting in the repression of anthocyanin biosynthesis. Our findings demonstrate a direct functional relationship between ABA signaling and the miR156-SBP-MBW complex regulatory module in driving drought-induced anthocyanin accumulation in grape berries.

Low-Dimensional-Materials-Based Photodetectors for Next-Generation Polarized Detection and Imaging.

The vector characteristics of light and the vectorial transformations during its transmission lay a foundation for polarized photodetection of objects, which broadens the applications of related detectors in complex environments. With the breakthrough of low-dimensional materials (LDMs) in optics and electronics over the past few years, the combination of these novel LDMs and traditional working modes is expected to bring new development opportunities in this field. Here, the state-of-the-art progress of LDMs, as polarization-sensitive components in polarized photodetection and even the imaging, is the main focus, with emphasis on the relationship between traditional working principle of polarized photodetectors (PPs) and photoresponse mechanisms of LDMs. Particularly, from the view of constitutive equations, the existing works are reorganized, reclassified, and reviewed. Perspectives on the opportunities and challenges are also discussed. It is hoped that this work can provide a more general overview in the use of LDMs in this field, sorting out the way of related devices for "more than Moore" or even the "beyond Moore" research.