CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity.

Targeting epigenetic regulators to potentiate anti-PD-1 immunotherapy converges on the activation of type I interferon (IFN-I) response, mimicking cellular response to viral infection, but how its strength and duration are regulated to impact combination therapy efficacy remains largely unknown. Here, we show that mitochondrial CPT1A downregulation following viral infection restrains, while its induction by epigenetic perturbations sustains, a double-stranded RNA-activated IFN-I response. Mechanistically, CPT1A recruits the endoplasmic reticulum-localized ZDHHC4 to catalyze MAVS Cys79-palmitoylation, which promotes MAVS stabilization and activation by inhibiting K48- but facilitating K63-linked ubiquitination. Further elevation of CPT1A incrementally increases MAVS palmitoylation and amplifies the IFN-I response, which enhances control of viral infection and epigenetic perturbation-induced antitumor immunity. Moreover, CPT1A chemical inducers augment the therapeutic effect of combined epigenetic treatment with PD-1 blockade in refractory tumors. Our study identifies CPT1A as a stabilizer of MAVS activation, and its link to epigenetic perturbation can be exploited for cancer immunotherapy.

A retrotransposon insertion in the Mao1 promoter results in erect pubescence and higher yield in soybean.

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity.

Tandemly duplicated MYB genes are functionally diverged in the regulation of anthocyanin biosynthesis in soybean.

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean (Glycine max) genome is characterized by a large number of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that 4 MYB genes (GmMYBA5, GmMYBA2, GmMYBA1, and Glyma.09g235000)-presumably generated by tandem duplication specifically in the Phaseoleae lineage-exhibited a stronger purifying selection in soybean compared to common bean (Phaseolus vulgaris). To gain insights into the diverse functions of these tandemly duplicated MYB genes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, induced metabolites, and evolutionary history of these 4 MYB genes. Our data revealed that Glyma.09g235000 is a pseudogene, while the remaining 3 MYB genes exhibit strong transcriptional activation activity, promoting anthocyanin biosynthesis in different soybean tissues. GmMYBA5, GmMYBA2, and GmMYBA1 induced anthocyanin accumulation by upregulating the expression of anthocyanin pathway-related genes. Notably, GmMYBA5 showed a lower capacity for gene induction compared to GmMYBA2 and GmMYBA1. Metabolomics analysis further demonstrated that GmMYBA5 induced distinct anthocyanin accumulation in Nicotiana benthamiana leaves and soybean hairy roots compared to GmMYBA2 and GmMYBA1, suggesting their functional divergence leading to the accumulation of different metabolites accumulation following gene duplication. Together, our data provide evidence of functional divergence within the MYB gene cluster following tandem duplication, which sheds light on the potential evolutionary directions of gene duplications during legume evolution.

Samarium-Oxo/Hydroxy Cluster: A Solar Photocatalyst for Chemoselective Aerobic Oxidation of Thiols for Disulfide Synthesis.

Oxidation contributes as a secondary driver of the prevailing carbon emission in the chemical industries. To address this issue, photocatalytic aerobic oxidation has emerged as a promising alternative. However, the challenge of achieving satisfactory chemoselectivity and effective use of solar light has hindered progress in this area. In this context, the present study introduces a novel homogeneous photocatalyst, [Sm6O(OH)8(H2O)24]I8(H2O)8 cluster (Sm-OC), via a unique auxiliary ligand-free oxidative hydrolysis. Using Sm-OC as catalyst, a solar photocatalyzed aerobic oxidation of thiols has been developed for the synthesis of valuable disulfides. Remarkably, this catalyst manifested a significant turnover number ≥2000 under tested conditions. Sm-OC-catalyzed aerobic oxidation showcased remarkable chemoselectivity. In thiol oxidations, despite the vulnerability of disulfides toward overoxidation, overoxidized byproducts or oxidation of nontarget functional groups was not detected across all 28 tested substrates. This investigation presents the first application of a lanthanide-oxo/hydroxy cluster in photocatalysis.

Photogenerated carrier dynamics of Mn2+ doped CsPbBr3 assembled with TiO2 systems: Effect of Mn doping content.

In recent years, all-inorganic perovskite materials have become an ideal choice for new thin film solar cells due to their excellent photophysical properties and have become a research hotspot. Studying the ultrafast dynamics of photo-generated carriers is of great significance for further improving the performance of such devices. In this work, we focus on the transient dynamic process of CsPbBr3/TiO2 composite systems with different Mn2+ doping contents using femtosecond transient absorption spectroscopy technology. We used singular value decomposition and global fitting to analyze the transient absorption spectra and obtained three components, which are classified as hot carrier cooling, charge transfer, and charge recombination processes, respectively. We found that the doping concentration of Mn2+ has an impact on all three processes. We think that the following two factors are responsible: one is the density of defect states and the other is the bandgap width of perovskite. As the concentration of doped Mn2+ increases, the charge transfer time constant shows a trend of initially increasing, followed by a subsequent decrease, reaching a turning point. This indicates that an appropriate amount of Mn2+ doping can effectively improve the photoelectric performance of solar cell systems. We proposed a possible charge transfer mechanism model and further elucidated the microscopic mechanism of the effect of Mn2+ doping on the interface charge transfer process of the CsPbBr3/TiO2 solar cell system.

Forensic age estimation in adults by pubic bone mineral density using multidetector computed tomography.

Radiology plays a crucial role in forensic anthropology for age estimation. However, most studies rely on morphological methods. This study aims to investigate the feasibility of using pubic bone mineral density (BMD) as a new age estimation method in the Chinese population. 468 pubic bone CT scans from living individuals in a Chinese hospital aged 18 to 87 years old were used to measure pubic BMD. The BMD of the bilateral pubic bone was measured using the Mimics software on cross-sectional CT images and the mean BMD of the bilateral pubic bone was also calculated. Regression analysis was performed to assess the correlation between pubic BMD and chronological age and to develop mathematical models for age estimation. We evaluated the accuracy of the best regression model using an independent validation sample by calculating the mean absolute error (MAE). Among all established models, the cubic regression model had the highest R2 value in both genders, with R2 = 0.550 for males and R2 = 0.634 for females. The results of the best model test showed that the MAE for predicting age using pubic BMD was 8.66 years in males and 7.69 years in females. This study highlights the potential of pubic BMD as a useful objective indicator for adult age estimation and could be used as an alternative in forensic practice when other better indicators are lacking.

Reductive Deuteration of Acyl Chlorides for the Synthesis of α,α-Dideuterio Alcohols Using SmI2 and D2O.

The synthesis of α,α-dideuterio alcohols has been achieved via single electron transfer reductive deuteration of acyl chlorides using SmI2 and D2O. This method is distinguished by its remarkable functional group tolerance and exquisite deuterium incorporation, which has also been applied to the synthesis of valuable deuterated agrochemicals and their building blocks.

Application of Iodine as a Catalyst in Aerobic Oxidations: A Sustainable Approach for Thiol Oxidations.

Iodine is a well-known oxidant that is widely used in organic syntheses. Thiol oxidation by stoichiometric iodine is one of the most commonly employed strategies for the synthesis of valuable disulfides. While recent advancements in catalytic aerobic oxidation conditions have eliminated the need for stoichiometric oxidants, concerns persist regarding the use of toxic or expensive catalysts. In this study, we discovered that iodine can be used as a cheap, low-toxicity catalyst in the aerobic oxidation of thiols. In the catalytic cycle, iodine can be regenerated via HI oxidation by O2 at 70 °C in EtOAc. This protocol harnesses sustainable oxygen as the terminal oxidant, enabling the conversion of primary and secondary thiols with remarkable efficiency. Notably, all 26 tested thiols, encompassing various sensitive functional groups, were successfully converted into their corresponding disulfides with yields ranging from >66% to 98% at a catalyst loading of 5 mol%.

Photocatalytic Dehalogenative Deuteration of Halides over a Robust Metal-Organic Framework.

Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal-organic framework, MFM-300(Cr), using CD3 CN as the deuterium source at room temperature. MFM-300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups. Synchrotron X-ray powder diffraction reveals the activation of halogenated substrates via confined binding within MFM-300(Cr). In situ electron paramagnetic resonance spectroscopy confirms the formation of carbon-based radicals as intermediates and reveals the reaction pathway. This protocol removes the use of precious-metal catalysts from state-of-the-art processes based upon direct hydrogen isotope exchange and shows high photocatalytic stability, thus enabling multiple catalytic cycles.

Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells.

Plasma levels of angiopoietin-2 are increased in patients with chronic kidney disease (CKD). Moreover, mouse models of progressive kidney disease also demonstrate increased angiopoietin-2 in both plasmas and kidneys. The role of dysregulated angiopoietins in the progression of kidney disease has not been thoroughly investigated. Here, we found in a cohort of 319 patients with CKD that plasma angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratios were positively associated with the development of kidney failure. In mice with progressive kidney disease induced by either ureteral obstruction or ischemia-reperfusion injury, overexpression of human angiopoietin-1 in the kidney tubules not only reduced macrophage infiltration in the initial stage post-injury but also attenuated endothelial cell apoptosis, microvascular rarefaction, and fibrosis in the advanced disease stage. Notably, angiopoietin-1 attenuated chemokine C-C motif ligand 2 (CCL2) expression in the endothelial cells of the fibrosing kidneys, and these protective effects led to attenuation of functional impairment. Mechanistically, angiopoietin-1 reduced CCL2-activated macrophage migration and protected endothelial cells against cell apoptosis induced by angiopoietin-2 and Wnt ligands. Based on this, we applied L1-10, an angiopoietin-2 inhibitor, to the mouse models of progressive kidney disease and found inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis. Thus, we defined the detrimental impact of increased angiopoietin-2 on kidney survival of patients with CKD which appears highlighted by angiopoietin-2 induced endothelial CCL2-activated macrophage infiltration and endothelial cell apoptosis in their kidneys undergoing fibrosis.

Suzuki-Miyaura Cross-Coupling of Aryl Fluorosulfonates Mediated by Air- and Moisture-stable [Pd(NHC)(µ-Cl)Cl]2 Precatalysts: Broad Platform for C-O Cross-Coupling of Stable Phenolic Electrophiles.

A highly efficient protocol for the Suzuki-Miyaura cross-coupling of aryl fluorosulfonates by selective -OF cleavage using well-defined, air- and moisture-stable NHC-Pd(II) chloro dimers is presented. The reaction proceeds in excellent yields and with broad functional group tolerance using 0.10-0.20 mol % of [Pd] in the presence of mild K3PO4 base under aqueous conditions. A variety of sensitive functional groups are tolerated in this operationally trivial protocol for C-O bond activation. Selectivity studies and gram scale cross-coupling are presented. The method advances well-defined and highly reactive Pd(II)-NHCs to the cross-coupling of readily available, orthogonal, and bench-stable fluorosulfonates as aryl halide surrogates.

Pathogenicity and genome-wide sequence analysis reveals relationships between soybean mosaic virus strains.

Soybean mosaic virus (SMV) is the most prevalent viral pathogen in soybean. In China, the SMV strains SC and N are used simultaneously in SMV resistance assessments of soybean cultivars, but the pathogenic relationship between them is unclear. In this study, SMV strains N1 and N3 were found to be the most closely related to SC18. Moreover, N3 was found to be more virulent than N1. A global pathotype classification revealed the highest level of genetic diversity in China. The N3 type was the most frequent and widespread worldwide, implying that SMV possibly originated in China and spread across continents through the dissemination of infected soybean. It also suggests that the enhanced virulence of N3 facilitated its spread and adaptability in diverse geographical and ecological regions worldwide. Phylogenetic analysis revealed prominent geographical associations among SMV strains/isolates, and genomic nucleotide diversity analysis and neutrality tests demonstrated that the whole SMV genome is under negative selection, with the P1 gene being under the greatest selection pressure. The results of this study will facilitate the nationwide use of SMV-resistant soybean germplasm and could provide useful insights into the molecular variability, geographical distribution, phylogenetic relationships, and evolutionary history of SMV around the world.

Myeloarchitectonic Asymmetries of Language Regions in the Human Brain.

One prominent theory in neuroscience and psychology assumes that cortical regions for language are left hemisphere lateralized in the human brain. In the current study, we used a novel technique, quantitative magnetic resonance imaging (qMRI), to examine interhemispheric asymmetries in language regions in terms of macromolecular tissue volume (MTV) and quantitative longitudinal relaxation time (T1) maps in the living human brain. These two measures are known to reflect cortical myeloarchitecture from the microstructural perspective. One hundred and fifteen adults (55 male, 60 female) were examined for their myeloarchitectonic asymmetries of language regions. We found that the cortical myeloarchitecture of inferior frontal areas including the pars opercularis, pars triangularis, and pars orbitalis is left lateralized, while that of the middle temporal gyrus, Heschl's gyrus, and planum temporale is right lateralized. Moreover, the leftward lateralization of myelination structure is significantly correlated with language skills measured by phonemic and speech tone awareness. This study reveals for the first time a mixed pattern of myeloarchitectonic asymmetries, which calls for a general theory to accommodate the full complexity of principles underlying human hemispheric specialization.

Alteration of Serum Metabolites in Women of Reproductive Age with Chronic Constipation.

BACKGROUND Chronic constipation is a common gastrointestinal disease. Our previous studies confirmed that there are differences in the composition and function of gut microbiota between women of reproductive age with chronic constipation and healthy controls. However, little is known about the differences in the metabolic profile of the 2 groups. The aim of this study was to observe changes in serum metabolites and identify potential metabolic pathways in the development of chronic constipation. MATERIAL AND METHODS A total of 50 participants were included in this study: 25 female patients of childbearing age with chronic constipation who met the inclusion and exclusion criteria and 25 healthy participants as a control group. Serum samples of these participants were collected; 1 portion of the serum sample was used for clinical biochemical analysis, and the other was used for non-targeted metabolomic testing. RESULTS Compared with the control group, serum 2-hydroxyphenylacetic acid levels were higher (P<0.05) and DL-phenylalanine levels were lower (P<0.05) in the constipation group. Other amino acids, such as 5-hydroxy-l-lysine and l-pipecolic acid, were upregulated, and L-valine, glycine, L-leucyl-L-proline, and N-formylmethionine were downregulated in the constipation group. In addition, levels of the bile acid, 3b-hydroxy-5-cholenoic acid, were higher in the constipation group than in the control group. Pathway analysis showed that the significantly altered pathways were phenylalanine metabolism and glycine, serine, and threonine metabolism. CONCLUSIONS These results strongly suggest that serum metabolites and pathways are significantly altered in women of reproductive age with chronic constipation.

Time-Frequency Mask-Aware Bidirectional LSTM: A Deep Learning Approach for Underwater Acoustic Signal Separation.

Underwater acoustic signal separation is a key technique for underwater communications. The existing methods are mostly model-based, and cannot accurately characterize the practical underwater acoustic communication environment. They are only suitable for binary signal separation and cannot handle multivariate signal separation. However, recurrent neural networks (RNNs) show a powerful ability to extract the features of temporal sequences. Inspired by this, in this paper, we present a data-driven approach for underwater acoustic signal separation using deep learning technology. We use a bidirectional long short-term memory (Bi-LSTM) approach to explore the features of a time-frequency (T-F) mask, and propose a T-F-mask-aware Bi-LSTM for signal separation. Taking advantage of the sparseness of the T-F image, the designed Bi-LSTM network is able to extract the discriminative features for separation, which further improves the separation performance. In particular, this method breaks through the limitations of the existing methods and not only achieves good results in multivariate separation but also effectively separates signals when they are mixed with 40 dB Gaussian noise signals. The experimental results show that this method can achieve a 97% guarantee ratio (PSR), and the average similarity coefficient of the multivariate signal separation is stable above 0.8 under high noise conditions. It should be noted that our model can only handle known signals such as test signals for calibration.

Identification of Competing Endogenous RNAs (ceRNAs) Network Associated with Drought Tolerance in Medicago truncatula with Rhizobium Symbiosis.

Drought, bringing the risks of agricultural production losses, is becoming a globally environmental stress. Previous results suggested that legumes with nodules exhibited superior drought tolerance compared with the non-nodule group. To investigate the molecular mechanism of rhizobium symbiosis impacting drought tolerance, transcriptome and sRNAome sequencing were performed to identify the potential mRNA-miRNA-ncRNA dynamic network. Our results revealed that seedlings with active nodules exhibited enhanced drought tolerance by reserving energy, synthesizing N-glycans, and medicating systemic acquired resistance due to the early effects of symbiotic nitrogen fixation (SNF) triggered in contrast to the drought susceptible with inactive nodules. The improved drought tolerance might be involved in the decreased expression levels of miRNA such as mtr_miR169l-5p, mtr_miR398b, and mtr_miR398c and its target genes in seedlings with active nodules. Based on the negative expression pattern between miRNA and its target genes, we constructed an mRNA-miR169l-ncRNA ceRNA network. During severe drought stress, the lncRNA alternative splicings TCONS_00049507 and TCONS_00049510 competitively interacted with mtr_miR169l-5p, which upregulated the expression of NUCLEAR FACTOR-Y (NF-Y) transcription factor subfamily NF-YA genes MtNF-YA2 and MtNF-YA3 to regulate their downstream drought-response genes. Our results emphasized the importance of SNF plants affecting drought tolerance. In conclusion, our work provides insight into ceRNA involvement in rhizobium symbiosis contributing to drought tolerance and provides molecular evidence for future study.

Sequential Iron-Catalyzed C(sp2)-C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols.

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp2)-C(sp3) cross-coupling with alkyl Grignard reagents that are prone to dimerization and ß-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C-N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis.

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D2O as a Deuterium Source.

Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.

Tandem H/D Exchange-SET Reductive Deuteration Strategy for the Synthesis of α,ß-Deuterated Amines Using D2O.

α,ß-Deuterated amines are crucial for the development of deuterated drugs. We intend to introduce the novel tandem H/D exchange-single electron transfer (SET) reductive deuteration strategy with high pot- and reagent-economy by the synthesis of α,ß-deuterated amine using nitrile as the precursor. The H/D exchange of the -CH2CN group was achieved by D2O/Et3N, which were also the required reagents in the tandem SmI2-mediated SET reductive deuteration of the α-deuterated nitrile. The potential application of this method was further showcased by the synthesis of bevantolol-d4.

A novel self-supported porous ZnO nanobelt arrays on Zn foils: excellent binder-free anode materials for LIBs.

ZnO is considered to be one of the promising anode materials for lithium-ion batteries (LIBs), but the poor electronic conductivity and large volume variation during lithium-ion extraction and insertion process of ZnO seriously hinders its commercial application in LIBs. In this study, we synthesized a novel self-supporting porous ZnO nanobelt (PZB) arrays on Zn foils, in which Zn foils can be directly used as current collectors to promote electrically connection between the active materials and the current collectors. Furthermore, the well-aligned ZnO nanobelts have a thin thickness and uniform porous structure, which endue it well improved electrochemical performance. The PZB anodes display a high areal capacity of 5.91 mAh cm-2at current density of 0.5 mA cm-2at room temperature, and deliver an areal capacity of 1.73 mAh cm-2at -20 °C, indicating its excellent application potential especially at low temperatures, and it makes the porous ZnO nanobelts a practical anode material for LIBs.