SlWRKY55 coordinately acts with SlVQ11 to enhance tomato thermotolerance by activating SlHsfA2.

High temperature (HT) severely restricts plant growth, development, and productivity. Plants have evolved a set of mechanisms to cope with HT, including the regulation of heat stress transcription factors (Hsfs) and heat shock proteins (Hsps). However, it is not clear how the transcriptional and translational levels of Hsfs and Hsps are controlled in tomato. Here, we reported that the HT-induced transcription factor SlWRKY55 recruited SlVQ11 to coordinately regulate defense against HT. SlWRKY55 directly bound to the promoter of SlHsfA2 and promoted its expression, which was increased by SlVQ11. Moreover, both SlWRKY55 and SlVQ11 physically interacted with SlHsfA2 to enhance the transcriptional activity of SlHsfA2. Thus, our results revealed a molecular mechanism that the SlWRKY55/SlVQ11-SlHsfA2 cascade enhanced thermotolerance and provided potential target genes for improving the adaptability of crops to HT.

MQ232, A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases.

BACKGROUND: Vaptans were developed at the end of the previous century as V2R antagonists. Tolvaptan is the most prescribed vaptan for hyponatremia and the autosomal polycystic kidney disease (ADPKD). However, its use is not as widespread as it should be due to price issues, a narrow therapeutic window and some side effects. With the aim of discovering new efficient and safer V2R antagonists, we screened animal venoms and identified several interesting peptide toxins. Among them, MQ1 displayed such unique biological properties in that regard that it was the starting point for the development of a potential drug candidate. METHODS: Human T-cell assays and bioinformatics was used to mitigate MQ1 immunogenicity risk. The MQ232 biodistribution in mice was done by positron emission tomography (PET). Pharmacodynamics, pharmacokinetics, acute and chronic toxicity tests were performed on control rats. A rat experimental model of dDAVP-induced hyponatremia, an ex vivo mice model of renal cysts and a mice orthologous model of ADPKD were used to validate MQ232 efficacy in these pathologies. RESULTS: Three mutations were introduced in MQ1 to mitigate its immunogenicity risk. A fourth gain-of-function mutation was added to generate MQ232. MQ232's safety was demonstrated by a first toxic dose as high as 3,000 nmol/kg and a strong kidney organ selectivity by PET imaging, while showing almost no interaction with the liver. MQ232's efficacy was first demonstrated with an effective dose of 3 nmol/kg in a hyponatremic model, and then in polycystic kidney models on which MQ232 significantly reduced cyst growth. CONCLUSIONS: We demonstrated, employing diverse translational techniques and minimizing animal use, MQ232's safety and efficacy in several rodent models of hyponatremia and ADPKD.

Ultrarapid Gelation of Porous Ti3C2Tx MXene Monoliths Induced by Ionic Liquids.

Gelation is a promising method to assemble 3D macroscopic structures from MXene sheets for various applications. However, the fine control and scalable manufacturing of 3D MXene monoliths remains a great challenge. Herein, the controllable gelation of Ti3C2Tx MXene initiated by various ionic liquids (ILs) is first proposed, where the IL serve as linkers to bond the nanosheets together through electrostatic and hydrogen bonding interactions, forming 3D monoliths with well-adjustable structure. Furthermore, density functional theory calculations and experiments further reveal the cross-linking effect of different ILs. Typically, 3D porous structure with high specific surface area, suitable pore size, and improved electrolyte affinity is designed through the cross-linking of Ti3C2Tx with 1-vinyl-3-ethylimidazole bromide ([C2VIm]Br-Ti3C2Tx). Due to the strong coupling, the as-synthesized monolith possesses excellent rate performance and high energy density. The methodology is quite flexible, controllable, and universal that provides a new perspective for promoting innovative applications of 2D materials.

Jasmonic acid enhances osmotic stress responses by MYC2-mediated inhibition of protein phosphatase 2C1 and response regulators 26 transcription factor in tomato.

The jasmonic acid (JA) signaling pathway is involved in the plant response to drought stress. JA and other hormones synergistically regulate the drought response in plants. However, the molecular mechanism underlying this synergism remains poorly defined. In the present study, transcriptome analyses of guard cells and quantitative PCR experiments revealed that MYC2 negatively regulated the negative regulator of ABA signaling, SlPP2C1, and the type-B response regulator in the cytokinin pathway, SlRR26, and this negative regulation was direct. SlRR26 overexpression reduced drought tolerance in transgenic tomatoes, whereas slrr26cr lines were more tolerant to drought. SlRR26 negatively modulated reactive oxygen species levels in stomata and stomatal closure through RobhB. Moreover, SlRR26 overexpression counteracted JA-mediated stomatal closure, suggesting that SlRR26 played a negative role in the JA-mediated drought response. These findings suggest that MYC2 plays a key role in JA-regulated stomatal closure under drought stress by inhibiting SlPP2C1 and SlRR26.

Sugar delivery at the tomato root and root galls after Meloidogyne incognita infestation.

Root-knot nematodes (RKNs) infect host plants and obtain nutrients such as sugars for their own development. Therefore, inhibiting the nutrient supply to RKNs may be an effective method for alleviating root-knot nematode disease. At present, the pathway by which sucrose is unloaded from the phloem cells to giant cells (GCs) in root galls and which genes related to sugar metabolism and transport play key roles in this process are unclear. In this study, we found that sugars could be unloaded into GCs only from neighboring phloem cells through the apoplastic pathway. With the development of galls, the contents of sucrose, fructose and glucose in the galls and adjacent tissue increased gradually. SUT1, SUT2, SWEET7a, STP10, SUS3 and SPS1 may provide sugar sources for GCs, while STP1, STP2 and STP12 may transport more sugar to phloem parenchyma cells. At the early stage of Meloidogyne incognita infestation, the sucrose content in tomato roots and leaves increased, while the glucose and fructose contents decreased. SWEET7a, SPS1, INV-INH1, INV-INH2, SUS1 and SUS3 likely play key roles in root sugar delivery. These results elucidated the pathway of sugar unloading in tomato galls and provided an important theoretical reference for eliminating the sugar source of RKNs and preventing root-knot nematode disease.

A Dual-Polythiophene Blending Strategy to Reduce the Efficiency-Stability-Cost Gap of Solar Cells.

Benefiting from the photovoltaic material innovation and delicate device optimization, high-efficiency solar cells employing polymeric materials are thriving. Reducing the gap of cost, efficiency, and stability is the critical challenge faced by the emerging solar cells such as organics, quantum dots and perovskites. Poly(3-alkylthiophene) demonstrates great potential in organic solar cells and quantum dot solar cells as the active layer or the hole transport layer due to its large scalability, excellent photoelectric performance, and favorable hydrophobicity. The present low efficiency and insufficient stability, restrict its commercial application. In this work, a facile strategy of blending two simple polythiophenes is put forward to manipulate the film microstructure and enhance the device efficiency and thermal stability of solar cells. The introduction of P3PT can improve the power conversion efficiency (PCE) of a benchmark cost-effective blend P3HT:O-IDTBR to 7.41%, and the developed ternary solar cells also exhibit increased thermal stability. More strikingly, the quantum dot solar cells with the dual-polythiophene hole transport layer achieve the highest PCE of 10.51%, which is among the topmost efficiencies for quantum dots/polythiophene solar cells. Together, this work provides an effective route to simultaneously optimize the device efficiency and thermal stability of solar cells.

The miR396a-SlGRF8 module regulates sugar accumulation in the roots via SlSTP10 during the interaction between root-knot nematodes and tomato plants.

Root-knot nematodes (RKNs; Meloidogyne spp.) are a serious threat to crop production. The competition between plants and pathogens for assimilates influences the outcome of their interactions. However, the mechanisms by which plants and nematodes compete with each other for assimilates have not been elucidated. In this study, we demonstrated that miR396a plays a negative role in defense against RKNs and a positive role in sugar accumulation in tomato roots. The overexpression of SlGRF8 (Solanum lycopersicum growth-regulating factor 8), the target of miR396a, decreased the sugar content of the roots and the susceptibility to RKNs, whereas the grf8-cr mutation had the opposite effects. Furthermore, we confirmed that SlGRF8 regulated the sugar content in roots by directly activating the transcription of SlSTP10 (Solanum lycopersicum sugar transporter protein 10) in response to RKN stress. Moreover, SlSTP10 was expressed primarily in the tissues surrounding giant cells, and the SlSTP10 knockout increased both the sugar content in the roots and the plant's susceptibility to RKNs. Overall, this study provides important insight into the molecular mechanism through which the miR396a-SlGRF8-SlSTP10 module regulates sugar allocation in roots under RKN stress.

Tomato defence against Meloidogyne incognita by jasmonic acid-mediated fine-tuning of kaempferol homeostasis.

Jasmonic acid (JA) is involved in the modulation of defence and growth activities in plants. The best-characterized growth-defence trade-offs stem from antagonistic crosstalk among hormones. In this study, we first confirmed that JA negatively regulates root-knot nematode (RKN) susceptibility via the root exudates (REs) of tomato plants. Omics and toxicological analyses implied that kaempferol, a type of flavonol, from REs has a negative effect on RKN infection. We demonstrated that SlMYB57 negatively regulated kaempferol contents in tomato roots, whereas SlMYB108/112 had the opposite effect. We revealed that JA fine-tuned the homeostasis of kaempferol via SlMYB-mediated transcriptional regulation and the interaction between SlJAZs and SlMYBs, thus ensuring a balance between lateral root (LR) development and RKN susceptibility. Overall, this work provides novel insights into JA-modulated LR development and RKN susceptibility mechanisms and elucidates a trade-off model mediated by JA in plants encountering stress.

SlVQ15 interacts with jasmonate-ZIM domain proteins and SlWRKY31 to regulate defense response in tomato.

Botrytis cinerea is one of the most widely distributed and harmful pathogens worldwide. Both the phytohormone jasmonate (JA) and the VQ motif-containing proteins play crucial roles in plant resistance to B. cinerea. However, their crosstalk in resistance to B. cinerea is unclear, especially in tomato (Solanum lycopersicum). In this study, we found that the tomato VQ15 was highly induced upon B. cinerea infection and localized in the nucleus. Silencing SlVQ15 using virus-induced gene silencing reduced resistance to B. cinerea. Overexpression of SlVQ15 enhanced resistance to B. cinerea, while disruption of SlVQ15 using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein9 (Cas9) technology increased susceptibility to B. cinerea. Furthermore, SlVQ15 formed homodimers. Additionally, SlVQ15 interacted with JA-ZIM domain proteins, repressors of the JA signaling pathway, and SlWRKY31. SlJAZ11 interfered with the interaction between SlVQ15 and SlWRKY31 and repressed the SlVQ15-increased transcriptional activation activity of SlWRKY31. SlVQ15 and SlWRKY31 synergistically regulated tomato resistance to B. cinerea, as silencing SlVQ15 enhanced the sensitivity of slwrky31 to B. cinerea. Taken together, our findings showed that the SlJAZ-interacting protein SlVQ15 physically interacts with SlWRKY31 to cooperatively control JA-mediated plant defense against B. cinerea.

Radiation-Induced Surface Modification of MXene with Ionic Liquid to Improve Electrochemical Properties and Chemical Stability.

For the first time, an ionic liquid was grafted onto Ti3C2Tx MXene interlayers (MXene-g-IL) using a radiation technique. The IL was tightly immobilized on the surface of MXene nanosheets via chemical linkage, which exhibited excellent specific capacitance (160 F g-1 at 5 mV s-1) and improved structural stability (maintaining the sheet-like structure for 180 days). The facile, efficient, and scalable synthetic strategy derived from the radiation technique can open a new avenue for covalent functionalization of MXene-based materials and promote their further application.

Fragmentation of SO2 q+ (q = 2-4) induced by 1 keV electron collision.

We report an investigation on the fragmentation dynamics of SO2 q+ (q = 2-4) induced by 1 keV electron collision utilizing an ion momentum imaging spectrometer. Six complete Coulomb explosion channels were observed using the time-of-flight correlation map. The kinetic energy release distributions for these channels were obtained and compared with those available in the literature. The fragmentation mechanisms of the three-body dissociation channels were analyzed by the Dalitz plots and Newton diagrams. Both concerted breakup and sequential fragmentation pathways were identified in the channel SO2 3+ → O+ + O+ + S+, whereas only the concerted breakup mechanism was confirmed for the channels SO2 4+ → O+ + O+ + S2+ and SO2 4+ → O2+ + O+ + S+. Using the Coulomb explosion model, we determined the molecular geometry from the concerted fragmentation channels, and the obtained bond lengths and angles from the higher kinetic energy release peaks are close to that of the neutral SO2 obtained by high-level quantum chemical calculation. The present results indicate that the electron impact experiment is a potential tool for the Coulomb explosion imaging of small molecules.

Pathways of two-body dissociation of BrCNq+ (q = 2, 3) induced by electron collision.

Pathways of two-body fragmentation of BrCNq+ (q = 2, 3) have been explored by combined experimental and theoretical studies. In the experiment, the BrCN molecule is ionized by 1 keV electron impact and the created fragment ions are detected using an ion momentum imaging spectrometer. Six two-body fragmentation channels are identified. By measuring the momentum vectors of the fragment ions, the kinetic energy release (KER) distributions for these channels have been determined. Theoretically, the potential energy curves of BrCNq+ (q = 2, 3) as a function of Br-C and C-N internuclear distances are calculated by the complete active space self-consistent field method. By comparing the measured KER and theoretical predictions, pathways for the fragmentation channels are assigned. The relative branching ratios of the channels are also determined.

The SlWRKY57-SlVQ21/SlVQ16 module regulates salt stress in tomato.

Salt stress is a major abiotic stress which severely hinders crop production. However, the regulatory network controlling tomato resistance to salt remains unclear. Here, we found that the tomato WRKY transcription factor WRKY57 acted as a negative regulator in salt stress response by directly attenuating the transcription of salt-responsive genes (SlRD29B and SlDREB2) and an ion homeostasis gene (SlSOS1). We further identified two VQ-motif containing proteins SlVQ16 and SlVQ21 as SlWRKY57-interacting proteins. SlVQ16 positively, while SlVQ21 negatively modulated tomato resistance to salt stress. SlVQ16 and SlVQ21 competitively interacted with SlWRKY57 and antagonistically regulated the transcriptional repression activity of SlWRKY57. Additionally, the SlWRKY57-SlVQ21/SlVQ16 module was involved in the pathway of phytohormone jasmonates (JAs) by interacting with JA repressors JA-ZIM domain (JAZ) proteins. These results provide new insights into how the SlWRKY57-SlVQ21/SlVQ16 module finely tunes tomato salt tolerance.

On-Surface Synthesis of Polyphenylene Wires Comprising Rigid Aliphatic Bicyclo[1.1.1]Pentane Isolator Units.

Bicyclo[1.1.1]pentane (BCP) motifs are of growing importance to the pharmaceutical industry as sp3 -rich bioisosteres of benzene rings and as molecular building blocks in materials science. Herein we explore the behavior of 1,3-disubstituted BCP moieties on metal surfaces by combining low-temperature scanning tunneling microscopy / non-contact atomic force microscopy studies with density functional theory modeling. We examine the configuration of individual BCP-containing precursors on Au(111), their supramolecular assembly and thermally activated dehalogenative coupling reactions, affording polymeric chains with incorporated electronically isolating units. Our studies not only provide the first sub-molecular insights of the BCP scaffold behavior on surfaces, but also extend the potential application of BCP derivatives towards integration in custom-designed surface architectures.

High-Spin (S = 1) Blatter-Based Diradical with Robust Stability and Electrical Conductivity.

Triplet ground-state organic molecules are of interest with respect to several emerging technologies but usually show limited stability, especially as thin films. We report an organic diradical, consisting of two Blatter radicals, that possesses a triplet ground state with a singlet-triplet energy gap, ΔEST ≈ 0.4-0.5 kcal mol-1 (2J/k ≈ 220-275 K). The diradical possesses robust thermal stability, with an onset of decomposition above 264 °C (TGA). In toluene/chloroform, glassy matrix, and fluid solution, an equilibrium between two conformations with ΔEST ≈ 0.4 kcal mol-1 and ΔEST ≈ -0.7 kcal mol-1 is observed, favoring the triplet ground state over the singlet ground-state conformation in the 110-330 K temperature range. The diradical with the triplet ground-state conformation is found exclusively in crystals and in a polystyrene matrix. The crystalline neutral diradical is a good electrical conductor with conductivity comparable to the thoroughly optimized bis(thiazolyl)-related monoradicals. This is surprising because the triplet ground state implies that the underlying π-system is cross-conjugated and thus is not compatible with either good conductance or electron delocalization. The diradical is evaporated under ultra-high vacuum to form thin films, which are stable in air for at least 18 h, as demonstrated by X-ray photoelectron and electron paramagnetic resonance (EPR) spectroscopies.

Systematic analysis of the sugar accumulation mechanism in sucrose- and hexose- accumulating cherry tomato fruits.

BACKGROUND: Sugar content is an important indicator of fruit quality. Except for a few wild tomato species that accumulate sucrose in the fruits, most cultivated tomato species accumulate hexose. Although several studies have focused on wild sucrose-accumulating tomato, the sucrose accumulation mechanism is still unclear. RESULTS: Here, two homozygous inbred cherry tomato lines ('TB0023' and 'TB0278', which accumulated sucrose and hexose, respectively) were selected to analyze the sugar accumulation mechanism. Carbohydrate analysis, cytological observation, gene expression and enzyme activity analysis and proteomics methods were used in this study. The results indicated that glucose and fructose were absolutely dominant in the soluble sugar content of hexose-accumulating cherry tomato fruit, while sucrose and a certain proportion of hexose were the main forms of soluble sugar in sucrose-accumulating cherry tomato fruit. The phloem unloading pathway of the hexose-accumulating cherry tomato fruit switched from symplastic to apoplastic during fruit development, and the sucrose-accumulating cherry tomato probably had a mixed unloading pathway involving the symplastic and apoplastic. High activity of acid invertase (AI), sucrose phosphate synthase (SPS), sucrose synthase (SS) and sugar transporters LeSUT1, SlSWEET2a and SlSWEET12c were important factors for hexose accumulation in the hexose-accumulating cherry tomato fruit, while LeSUT2, SPS, SS, SlSWEET1b, SlSWEET5b, SlSWEET11b, SlSWEET7a, SlSWEET14 were responsible for solute sugar accumulation in the sucrose-accumulating cherry tomato. CONCLUSIONS: This study provides detailed evidence for elucidation of the tomato sugar accumulation mechanism from the perspective of cell structure, physiology and molecular biology, providing a theoretical basis for the improvement of tomato quality and aiding the utilization of tomato genetic resources.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery.

BACKGROUND: The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladder-preserving surgery. This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence. METHODS: The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected. The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis. A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables. The C-index, receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence. RESULTS: During the follow-up period, a total of 65 patients experienced gallstone recurrence, and the recurrence rate was 35.5%. Multivariate logistic regression analysis revealed that the course of gallstones > 2 years [odds ratio (OR) = 2.567, 95% confidence interval (CI): 1.270-5.187, P = 0.009], symptomatic gallstones (OR = 2.589, 95% CI: 1.059-6.329, P = 0.037), multiple gallstones (OR = 2.436, 95% CI: 1.133-5.237, P = 0.023), history of acute cholecystitis (OR = 2.778, 95% CI: 1.178-6.549, P = 0.020) and a greasy diet (OR = 2.319, 95% CI: 1.186-4.535, P = 0.014) were independent risk factors for gallstone recurrence after gallbladder-preserving surgery. A nomogram model for predicting the recurrence of gallstones was established based on the above five variables. The results showed that the C-index of the nomogram model was 0.692, suggesting it was valuable to predict gallstone recurrence. Moreover, the calibration curve showed good consistency between the predicted probability and actual probability. CONCLUSIONS: The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones. Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

Thermoelectric Performance of Lead-Free Two-Dimensional Halide Perovskites Featuring Conjugated Ligands.

Sn-based halide perovskites are promising for thermoelectric (TE) device applications because of their high electrical conductivity as well as the low thermal conductivity associated with their soft lattices. However, conventional three-dimensional Sn-based perovskites are not stable under typical TE device operating conditions. Here, we report a stable two-dimensional Sn-based perovskite for thermoelectric energy conversion by incorporating bulky conjugated ligands. We demonstrate a thin film with a large power factor of 5.42 ± 3.07 (average) and 7.07 (champion) µW m-1 K-2 at 343 K with an electrical conductivity of 5.07 S cm-1 and a Seebeck coefficient of 118.1 µV K-1. Importantly, these thin films show excellent operational stability (i.e., for over 100 h) at 313 K. This work suggests that the novel hybrid two-dimensional perovskites are a promising platform for thermoelectric energy conversion applications.

The Effect of tRNA[Ser]Sec Isopentenylation on Selenoprotein Expression.

Transfer RNA[Ser]Sec carries multiple post-transcriptional modifications. The A37G mutation in tRNA[Ser]Sec abrogates isopentenylation of base 37 and has a profound effect on selenoprotein expression in mice. Patients with a homozygous pathogenic p.R323Q variant in tRNA-isopentenyl-transferase (TRIT1) show a severe neurological disorder, and hence we wondered whether selenoprotein expression was impaired. Patient fibroblasts with the homozygous p.R323Q variant did not show a general decrease in selenoprotein expression. However, recombinant human TRIT1R323Q had significantly diminished activities towards several tRNA substrates in vitro. We thus engineered mice conditionally deficient in Trit1 in hepatocytes and neurons. Mass-spectrometry revealed that hypermodification of U34 to mcm5Um occurs independently of isopentenylation of A37 in tRNA[Ser]Sec. Western blotting and 75Se metabolic labeling showed only moderate effects on selenoprotein levels and 75Se incorporation. A detailed analysis of Trit1-deficient liver using ribosomal profiling demonstrated that UGA/Sec re-coding was moderately affected in Selenop, Txnrd1, and Sephs2, but not in Gpx1. 2'O-methylation of U34 in tRNA[Ser]Sec depends on FTSJ1, but does not affect UGA/Sec re-coding in selenoprotein translation. Taken together, our results show that a lack of isopentenylation of tRNA[Ser]Sec affects UGA/Sec read-through but differs from a A37G mutation.

Ribosome profiling of selenoproteins in vivo reveals consequences of pathogenic Secisbp2 missense mutations.

Recoding of UGA codons as selenocysteine (Sec) codons in selenoproteins depends on a selenocysteine insertion sequence (SECIS) in the 3'-UTR of mRNAs of eukaryotic selenoproteins. SECIS-binding protein 2 (SECISBP2) increases the efficiency of this process. Pathogenic mutations in SECISBP2 reduce selenoprotein expression and lead to phenotypes associated with the reduction of deiodinase activities and selenoprotein N expression in humans. Two functions have been ascribed to SECISBP2: binding of SECIS elements in selenoprotein mRNAs and facilitation of co-translational Sec insertion. To separately probe both functions, we established here two mouse models carrying two pathogenic missense mutations in Secisbp2 previously identified in patients. We found that the C696R substitution in the RNA-binding domain abrogates SECIS binding and does not support selenoprotein translation above the level of a complete Secisbp2 null mutation. The R543Q missense substitution located in the selenocysteine insertion domain resulted in residual activity and caused reduced selenoprotein translation, as demonstrated by ribosomal profiling to determine the impact on UGA recoding in individual selenoproteins. We found, however, that the R543Q variant is thermally unstable in vitro and completely degraded in the mouse liver in vivo, while being partially functional in the brain. The moderate impairment of selenoprotein expression in neurons led to astrogliosis and transcriptional induction of genes associated with immune responses. We conclude that differential SECISBP2 protein stability in individual cell types may dictate clinical phenotypes to a much greater extent than molecular interactions involving a mutated amino acid in SECISBP2.