New genetic resources for aphid resistance were identified from a newly developed wheat mutant library.

Reports on development of resilient wheat mutants to aphid infestation-causing heavy losses to wheat production in many parts of the world, are scanty. The present study aimed to identify genetic diversity of wheat mutants in terms of varying degree of resistance to aphid infestation which can help protect wheat crop, improve yields and enhance food security. Resistance response to aphid infestation was studied on newly developed 33 wheat mutants, developed through irradiating seed of an elite wheat cultivar "Punjab-11" with gamma radiations, during three normal growing seasons at two sites. Data on various traits including aphid count per plant, biochemical traits, physiological traits and grain yield was recorded. Meteorological data was also collected to unravel the impact of environmental conditions on aphid infestation on wheat plants. Minimum average aphid infestation was found on Pb-M-2725, Pb-M-2550, and Pb-M-2719 as compared to the wild type. High yielding mutants Pb-M-1323, Pb-M-59, and Pb-M-1272 supported the moderate aphid infestation. The prevailing temperature up to 25 °C showed positive correlation (0.25) with aphid count. Among biochemical traits, POD (0.34), TSP (0.33), TFA (0.324) exhibited a high positive correlation with aphid count. In addition, CAT (0.31), TSS (0.294), and proline content (0.293) also showed a positive correlation with aphid count. However, all physiological traits depicted negative correlation with aphid count, while, a very weak correlation (0.12) was found between mean aphid count and grain yield. In PCA biplots, the biochemical variables clustered together with aphid count, while physiological variables grouped with grain yield. Biochemical parameters contributed most, towards first dimension of the PCA (48.6%) as compared to the physiological variables (13%). The FAMD revealed that mutant lines were major contributor towards total variation; Pb-M-1027, Pb-M-1323, Pb-M-59 were found to be the most diverse lines. The PCA revealed that biochemical parameters played a significant role in explaining variations in aphid resistance, emphasizing their importance in aphid defense mechanisms. The identified mutants can be utilized by the international wheat community for getting insight into the molecular circuits of resistant mechanism against aphids as well as for designing new KASP markers. This study also highlights the importance of considering both genetic and environmental factors in the development of resilient wheat varieties and pave the way for further investigations into the molecular mechanisms underpinning aphid resistance in wheat.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

Ferroptosis as a potential therapeutic target for age-related macular degeneration.

Cell death plays a crucial part in the process of age-related macular degeneration (AMD), but its mechanisms remain elusive. Accumulating evidence suggests that ferroptosis, a novel form of regulatory cell death characterized by iron-dependent accumulation of lipid hydroperoxides, has a crucial role in the pathogenesis of AMD. Numerous studies have suggested that ferroptosis participates in the degradation of retinal cells and accelerates the progression of AMD. Furthermore, inhibitors of ferroptosis exhibit notable protective effects in AMD, underscoring the significance of ferroptosis as a pivotal mechanism in the death of retinal cells during the process of AMD. This review aims to summarize the molecular mechanisms of ferroptosis in AMD, enumerate potential inhibitors and discuss the challenges and future opportunities associated with targeting ferroptosis as a therapeutic strategy, providing important information references and insights for the prevention and treatment of AMD.

Electronic Effect Promoted Visible-Light-Driven CO2-to-CO Conversion in a Water-Containing System.

The design of unsaturated nonprecious metal complexes with high catalytic performance for photochemical CO2 reduction is still an important challenge. In this paper, four coordinatively unsaturated Co-salen complexes 1-4 were explored in situ using o-phenylenediamine derivatives and 5-methylsalicylaldehyde as precursors of the ligands in 1-4. It was found that complex 4, bearing a nitro substituent (-NO2) on the aromatic ring of the salen ligand, exhibits the highest photochemical performance for visible-light-driven CO2-to-CO conversion in a water-containing system, with TONCO and CO selectivity values of 5300 and 96%, respectively. DFT calculations and experimental results revealed that the promoted photocatalytic activity of 4 is ascribed to the electron-withdrawing effect of the nitro group in 4 compared to 1-3 (with -CH3, -F, and -H groups, respectively), resulting in a lower reduction potential of active metal centers CoII and lower barriers for CO2 coordination and C-O cleavage steps for 4 than those for catalysts 1-3.

Cobalt-based tripodal complexes as molecular catalysts for photocatalytic CO2 reduction.

Construction of artificial photosynthetic systems including CO2 reduction is a promising pathway to produce carbon-neutral fuels and mitigate the greenhouse effect concurrently. However, the exploitation of earth-abundant catalysts for photocatalytic CO2 reduction remains a fundamental challenge, which can be assisted by a systematic summary focusing on a specific catalyst family. Cobalt-based complexes featuring tripodal ligands should merit more insightful discussion and summarization, as they are one of the most examined catalyst families for CO2 photoreduction. In this feature article, the key developments of cobalt-based tripodal complexes as molecular catalysts for light-driven CO2 reduction are discussed to offer an upcoming perspective, analyzing the present progress in electronic/steric tuning through ligand modification and dinuclear design to achieve a synergistic effect, as well as the bottlenecks for further development.

Nanoreactor-based catalytic systems for therapeutic applications: Principles, strategies, and challenges.

Inspired by natural catalytic compartments, various synthetic compartments that seclude catalytic reactions have been developed to understand complex multistep biosynthetic pathways, bestow therapeutic effects, or extend biosynthetic pathways in living cells. These emerging nanoreactors possessed many advantages over conventional biomedicine, such as good catalytic activity, specificity, and sustainability. In the past decade, a great number of efficient catalytic systems based on diverse nanoreactors (polymer vesicles, liposome, polymer micelles, inorganic-organic hybrid materials, MOFs, etc.) have been designed and employed to initiate in situ catalyzed chemical reactions for therapy. This review aims to present the recent progress in the development of catalytic systems based on nanoreactors for therapeutic applications, with a special emphasis on the principles and design strategies. Besides, the key components of nanoreactor-based catalytic systems, including nanocarriers, triggers or energy inputs, and products, are respectively introduced and discussed in detail. Challenges and prospects in the fabrication of therapeutic catalytic nanoreactors are also discussed as a conclusion to this review. We believe that catalytic nanoreactors will play an increasingly important role in modern biomedicine, with improved therapeutic performance and minimal side effects.

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

Background: Lung cancer remains a major global health challenge. Macrophages (Macs) are one important component of tumor microenvironments (TMEs); however, their prognostic relevance to lung cancer is currently unknown due to the complexity of their phenotypes. Methods: In the present study, reanalysis and atlas reconstruction of downloaded single-cell RNA sequencing (scRNAseq) data were used to systematically compare the component and transcriptional changes in Mac subtypes across different stages of lung cancer. Results: We found that with the progression of lung cancer, the proportion of alveolar macrophages (aMacs) gradually decreased, while the proportions of Macs and monocytes (Monos) gradually increased, suggesting a chemotaxis process followed by a Mono-Mac differentiation process. Meanwhile, through ligand-receptor (LR) screening, we identified 9 Mac-specific interactions that were enriched during the progression and metastasis of lung cancer, which could potential promote M2 polarization or the infiltration of M2 Macs. Moreover, we found that the expression of SPP1 in Macs increased with lung cancer progression, and identified 9 genes that were correlated with the expression of SPP1 in Macs, which might also contribute to the immunosuppression process in lung cancer. Conclusions: Our results revealed detailed changes in Macs at different stages of lung cancer progression and metastasis and provided potential therapeutic targets that could be used in future lung cancer treatments.

Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.

Identification of KASP markers and candidate genes for drought tolerance in wheat using 90K SNP array genotyping of near-isogenic lines targeting a 4BS quantitative trait locus.

KEY MESSAGE: This study identified a novel SNP and developed a highly efficient KASP marker for drought tolerance in wheat by genotyping NILs targeting a major QTL for drought tolerance using an SNP array and validation with commercial varieties. Common wheat (Triticum aestivum L.) is an important winter crop worldwide and a typical allopolyploid with a large and complex genome. With global warming, the environmental volatility and incidence of drought in wheat-producing areas will increase. Molecular markers for drought tolerance are urgently needed to enhance drought tolerance breeding. Here, we genotyped four near-isogenic line (NIL) pairs targeting a major QTL qDSI.4B.1 on wheat chromosome arm 4BS for drought tolerance using the 90K SNP Illumina iSelect array and discovered a single nucleotide polymorphism (SNP) (Excalibur_c100336_106) with consistent genotype-phenotype associations among all four NIL pairs and their parents. Then, we converted the SNP into a Kompetitive Allele-Specific PCR (KASP) marker, with an accuracy of 100% for the four NIL pairs and their parents and as high as 81.8% for the 44 tested wheat lines with known phenotypes collected from Australia and China. Two genes near this SNP were suggested as candidate genes for drought tolerance in wheat after checking the Chinese Spring reference genome annotation version 1.1. One gene, TraesCS4B02G085300, encodes an F-box protein reportedly related to the ABA network, a main pathway for drought tolerance, and another gene, TraesCS4B02G085400, encodes a calcineurin-like metallophos-phoesterase transmembrane protein, which participates in Ca2+-dependent phosphorylation regulatory system. Based on this work and previous research on pre-harvest sprouting, we established a quick and efficient general SQV-based approach for KASP marker development, integrating genotyping by SNP arrays (S) using NILs targeting major QTL for a specific trait (Q) and validating them with commercial varieties (V). The identified SNP and developed KASP marker could be applied to marker-assisted selection in drought breeding, and further study of the candidate genes may improve our understanding of drought tolerance in wheat.

Russian Doll-like 3d-4f Cluster Wheels with Slow Relaxation of Magnetization.

The solvothermal reactions of LnCl3·6H2O and MCl2·6H2O (M = Co, Ni) with 2,2'-diphenol (H2L1) and 5,7-dichloro-8-hydroxyquinoline (HL2) gave three 3d-4f heterometallic wheel-like nano-clusters [Ln7M6(L1)6(L2)6(µ3-OH)6(OCH3)6Cl(CH3CN)6]Cl2·xH2O (Ln = Dy, M = Co, x = 3 for 1; Ln = Dy, M = Ni, x = 0 for 2; Ln = Tb, M = Ni, x = 0 for 3) with similar cluster structure. The innermost Ln(III) ion is encapsulated in a planar Ln6 ring which is further embedded in a chair-conformation M6 ring, constructing a Russian doll-like 3d-4f cluster wheel Ln(III)⸦Ln6⸦M6. 2 and 3 show obvious slow magnetic relaxation behavior with negligible opening of the magnetic hysteresis loop. Such a Russian doll-like 3d-4f cluster wheel with the lanthanide disc isolated by transition metallo-ring is rarely reported.

NOTCH4ΔL12_16 sensitizes lung adenocarcinomas to EGFR-TKIs through transcriptional down-regulation of HES1.

Resistance to epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) remains one of the major challenges in lung adenocarcinoma (LUAD) therapy. Here, we find an increased frequency of the L12_16 amino acid deletion mutation in the signal peptide region of NOTCH4 (NOTCH4ΔL12_16) in EGFR-TKI-sensitive patients. Functionally, exogenous induction of NOTCH4ΔL12_16 in EGFR-TKI -resistant LUAD cells sensitizes them to EGFR-TKIs. This process is mainly mediated by the reduction of the intracellular domain of NOTCH4 (NICD4) caused by the NOTCH4ΔL12_16 mutation, which results in a lower localization of NOTCH4 in the plasma membrane. Mechanistically, NICD4 transcriptionally upregulates the expression of HES1 by competitively binding to the gene promoter relative to p-STAT3. Because p-STAT3 can downregulate the expression of HES1 in EGFR-TKI-resistant LUAD cells, the reduction of NICD4 induced by NOTCH4ΔL12_16 mutation leads to a decrease in HES1. Moreover, inhibition of the NOTCH4-HES1 pathway using inhibitors and siRNAs abolishes the resistance of EGFR-TKI. Overall, we report that the NOTCH4ΔL12_16 mutation sensitizes LUAD patients to EGFR-TKIs through transcriptional down-regulation of HES1 and that targeted blockade of this signaling cohort could reverse EGFR-TKI -resistance in LUAD, providing a potential approach to overcome resistance to EGFR-TKI -therapy.

Periodic changes in chain lengths distribution parameters of wheat starch during endosperm development.

This study analyzed the molecular structure of developing wheat endosperm starch at different stages after anthesis (DAA) using chain length distribution analysis by size exclusion chromatography (SEC) and fluorophore-assisted carbohydrate electrophoresis. Our results revealed periodic changes in the content of both amylose and amylopectin fractions. Specifically, the content of amylose chains with a degree of polymerization (DP) > 100 significantly decreased from 5 to 10 DAA (28% to 21%) and from 15 to 20 DAA (29% to 26%), but increased between 10 and 15 DAA (21% to 29%) and 20 to 25 DAA (30.0% to 33%). Conversely, the content of short amylopectin chains with DP ≤ 32 showed the opposite trend. Interestingly, mRNA expression levels of key starch biosynthesis genes did not exhibit periodic changes. These findings contribute to our understanding of starch biosynthesis and provide important insights for the development of starch-based products.

Diversification of three TaSOS1 genes and their roles in sodium exclusion in bread wheat (Triticum aestivum L.).

The ability to exclude sodium from the shoot is a crucial feature of salinity tolerance in bread wheat (Triticum aestivum L.). The plasma membrane sodium/proton exchanger salt-overly-sensitive 1 (SOS1) is a critical Na+. efflux protein in plants. Here, we cloned three homologues of the TaSOS1 gene in bread wheat, designated TaSOS1-A1, TaSOS1-B1 and TaSOS1-D1, respectively, according to the location on group 3 chromosomes 3A, 3B and 3D. Sequence analysis demonstrated that the TaSOS1 deduced protein-contained domains similar to the SOS1 protein, including 12 membrane-spanning regions, a long hydrophilic tail in the C-terminus, the cyclic nucleotidebinding domain, the putative auto-inhibitory domain and the phosphorylation motif. Phylogenetic analysis established the evolutionary relationships between the different copies of this gene in bread wheat and its diploid progenitors, as well as with SOS1 genes from Arabidopsis, rice and Brachypodium distachyon. Analysis of transient TaSOS1-A1::green fluorescent protein expression demonstrated that TaSOS1 was exclusively localized to the plasma membrane. The yeast and Arabidopsis complementary test supported the sodium extrusion function of TaSOS1-A1. Virus-induced gene silencing technology was used to further examine the function of TaSOS1-A1 in bread wheat.

Identification of major QTLs for yield-related traits with improved genetic map in wheat.

Introduction: Identification of stable major quantitative trait loci (QTLs) for yield-related traits is important for yield potential improvement in wheat breeding. Methods: In the present study, we genotyped a recombinant inbred line (RIL) population using the Wheat 660K SNP array and constructed a high-density genetic map. The genetic map showed high collinearity with the wheat genome assembly. Fourteen yield-related traits were evaluated in six environments for QTL analysis. Results and Discussion: A total of 12 environmentally stable QTLs were identified in at least three environments, explaining up to 34.7% of the phenotypic variation. Of these, QTkw-1B.2 for thousand kernel weight (TKW), QPh-2D.1 (QSl-2D.2/QScn-2D.1) for plant height (PH), spike length (SL) and spikelet compactness (SCN), QPh-4B.1 for PH, and QTss-7A.3 for total spikelet number per spike (TSS) were detected in at least five environments. A set of Kompetitive Allele Specific PCR (KASP) markers were converted based on the above QTLs and used to genotype a diversity panel comprising of 190 wheat accessions across four growing seasons. QPh-2D.1 (QSl-2D.2/QScn-2D.1), QPh-4B.1 and QTss-7A.3 were successfully validated. Compared with previous studies, QTkw-1B.2 and QPh-4B.1 should be novel QTLs. These results provided a solid foundation for further positional cloning and marker-assisted selection of the targeted QTLs in wheat breeding programs.

Electronic effects promoted the catalytic activities of binuclear Co(II) complexes for visible-light-driven CO2 reduction in a water-containing system.

Under the action of a catalyst, the photoinduced reduction of CO2 to chemicals and fuels is one of the greenest and environment-friendly approaches for decreasing atmospheric CO2 emissions. Since the environment was affected by the greenhouse effect, scientists have never stopped exploring efficient photoinduced CO2 reduction systems, particularly the highly desired non-noble metal complexes. Most of the currently reported complexes based on non-noble metals exhibit low catalytic activity, selectivity, and stability in aqueous systems under the irradiation of visible light. Herein, we report a new binuclear cobalt complex [Co2(L1)(OAc)2](OAc) (Co2L1, HL1 = 2,6-bis((bis(pyridin-2-ylmethyl)amino)methyl)-4-methoxyphenol), which accelerates the visible-light-driven conversion of CO2 to CO in acetonitrile/water (4/1, v/v) nearly 40% more than that for the previously reported [Co2(L2)(OAc)2](OAc) (Co2L2, HL2 = 2, 6-bis((bis(pyridin-2-ylmethyl)amino)methyl)-4-(tert-butyl)phenol) by our research group. It has an excellent CO selectivity of 98%, and the TONCO is as high as 5920. Experimental results and DFT calculations showed that the enhanced catalytic performance of Co2L1 is due to the electron-donating effect of a methoxy group (-OCH3) in Co2L1 compared to a tertiary butyl group (-C(CH3)3) in Co2L2, which reduces the energy barrier of the rate-limiting CO2 coordination step in the visible-light-driven CO2 reduction process.

Identification of a Wheat Powdery Mildew Dominant Resistance Gene in the Pm5 Locus for High-Throughput Marker-Assisted Selection.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), poses a severe threat to wheat yield and quality worldwide. Rapid identification and the accurate transference of effective resistance genes are important to the development of resistant cultivars and the sustainable control of this disease. In the present study, the wheat line AL11 exhibited high levels of resistance to powdery mildew at both the seedling and adult plant stages. Genetic analysis of the AL11 × 'Shixin 733' mapping population revealed that its resistance was controlled by a single dominant gene, tentatively designated PmAL11. Using bulked segregant RNA-Seq and molecular marker analysis, PmAL11 was mapped to the Pm5 locus on chromosome 7B where it cosegregated with the functional marker Pm5e-KASP. Sequence alignment analysis revealed that the Pm5e-homologous sequence in AL11 was identical to the reported recessive gene Pm5e in wheat landrace 'Fuzhuang 30'. It appears that PmAL11 was most probably Pm5e, but it was mediated by a dominant inheritance pattern, so it should provide a valuable resistance resource for both genetic study and wheat breeding. To efficiently use and trace PmAL11 in breeding, a new kompetitive allele-specific PCR marker AL11-K2488 that cosegregated with this gene was developed and confirmed to be applicable in the different wheat backgrounds, thus promoting its use in the marker-assisted selection of PmAL11.

Identification and validation of plant height, spike length and spike compactness loci in common wheat (Triticum aestivum L.).

BACKGROUND: Plant height (PH), spike length (SL) and spike compactness (SCN) are important agronomic traits in wheat due to their strong correlations with lodging and yield. Thus, dissection of their genetic basis is essential for the improvement of plant architecture and yield potential in wheat breeding. The objective of this study was to map quantitative trait loci (QTL) for PH, SL and SCN in a recombinant inbred line (RIL) population derived from the cross 'PuBing3228 × Gao8901' (PG-RIL) and to evaluate the potential values of these QTL to improve yield. RESULTS: In the current study, Five, six and ten stable QTL for PH, SL, and SCN, respectively, were identified in at least two individual environments. Five major QTL QPh.cas-5A.3, QPh.cas-6A, QSl.cas-6B.2, QScn.cas-2B.2 and QScn.cas-6B explained 5.58-25.68% of the phenotypic variation. Notably, two, three and three novel stable QTL for PH, SL and SCN were identified in this study, which could provide further insights into the genetic factors that shape PH and spike morphology in wheat. Conditional QTL analysis revealed that QTL for SCN were mainly affected by SL. Moreover, a Kompetitive Allele Specific PCR (KASP) marker tightly linked to stable major QTL QPh.cas-5A.3 was developed and verified using the PG-RIL population and a natural population. CONCLUSIONS: Twenty-one stable QTL related to PH, SL, and SCN were identified. These stable QTL and the user-friendly marker KASP8750 will facilitate future studies involving positional cloning and marker-assisted selection in breeding.

Highly Efficient Visible-Light-Driven CO2-to-CO Conversion by Coordinatively Unsaturated Co-Salen Complexes in a Water-Containing System.

The development of cost-effective catalysts for CO2 reduction is highly desired but remains a significant challenge. The unsaturated coordination metal center in a catalyst is favorable for the process of catalytic CO2 reduction. In this paper, two asymmetric salen ligands were used to synthesize two coordinatively unsaturated Co-salen complexes. The two Co-salen complexes exhibit an unsaturated coordination pattern and display high activity and CO selectivity for visible-light-driven CO2 reduction in a water-containing system. The photocatalytic performance of 2 is higher than that of 1 because the reduction potential of the catalytic CoII center and the energy barrier of the catalytic transition states of 2 are lower than those of 1, with turnover numbers (TONCO), turnover frequencies (TOF), and CO selectivity values of 8640, 0.24 s-1, and 97% for 2, respectively. The photocatalytic reduction of CO2 to CO for 2 is well supported by control experiments and density functional theory (DFT) calculations.

Synthesis and antitumor activities of five Cu(II) complexes of bis(5-halosalicylidene)-1,3-propanediamine derivatives.

The development of metal complexes of Schiff base has attracted much attention due to their DNA binding properties and extensive biological activities. We reported here five copper(II) complexes [Cu(L1)] (1), [Cu(L2)] (2), [Cu(L3)] (3), [Cu2(L4)(OAc)] (4), and [Cu2(L5)(HCOO)] (5) bearing the bis-Schiff base ligands of bis(5-chlorosalicylidene)-1,3-propanediamine (H2L1), bis(5-chlorosalicylidene)-2-methyl-1,3-propanediamine (H2L2), bis(5-bromosalicylidene)-2-methyl-1,3-propanediamine (H2L3), bis(5-chlorosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L4), and bis(5-bromosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L5), respectively. The single crystal X-ray diffraction analysis results revealed that complexes 1-3 present mononuclear structures and complexes 4 and 5 show dinuclear structures. It was also shown that all of these complexes are stable under physiological conditions. The in vitro antitumor activities of the five complexes were evaluated. Anticancer selectivity was also found for complex 2 on different cell lines with the lowest IC50 value on Hela cells. Further mechanistic studies showed that the three mononuclear Cu(II) complexes can induce apoptosis through the mitochondrial pathway by decreasing mitochondrial membrane potential and increasing the reactive oxygen species (ROS) and Ca2+ levels. They can activate caspase-3 and caspase-9, and can also regulate the expression of pro-apoptotic protein and anti-apoptotic protein in cells. All of these results showed that complex 2 is a potential anticancer drug.

Integrated transcriptomic and metabolomic analyses revealed the regulatory mechanism of sulfur application in grain yield and protein content in wheat (Triticum aestivum L.).

Sulfur fertilizers play an important role in increasing the yield and improving the dough quality of bread wheat, but their regulatory mechanism remains unclear. In this study, 0 kg·ha-1 (S0) and 60 kg·ha-1 (S60) of sulfur were applied on the anthesis date; subsequently, immature wheat grains at 8, 13, and 18 days post-anthesis (DPA) were subjected to integrated transcriptomic and metabolomic analyses to investigate the changes in the gene/metabolite activity in a typical strong-gluten wheat, Gaoyou2018 (GY2018). Our data show that the S60 treatment could significantly increase the grain yield and grain protein content by 13.2 and 3.6%, respectively. The transcriptomic analysis revealed that 10,694 differentially expressed genes (DEGs) were induced by S60 from 8 to 18 DPA when compared with their corresponding no-sulfur controls, and most DEGs were mainly involved in lipid metabolism and amino acid metabolism pathways. Ninety-seven MYB transcription factors (TFs) were identified as responsive to the S60 treatment; of these, 66 showed significantly differential expression at 13 DPA, and MYB118 might participate in the process of sulfur metabolism by regulating glucosinolate synthesis. In total, 542 significantly enriched differentially expressed (DE) metabolites (DEMs) were identified following the S60 treatment, which mainly included secondary metabolites, carbohydrates, and amino acids. Several metabolites (e.g., glutathione, sucrose, GDP-alpha-D-glucose, and amino acids) exhibited altered abundances following the S60 treatment. The combination of transcriptomic and metabolomic analyses highlighted the important role of amino acid metabolism (especially cysteine, methionine, and glutathione metabolism) and starch and sucrose metabolism pathways after S60 application. Our results provide valuable information enhancing our understanding of the molecular mechanism of the response to sulfur and provide useful clues for grain protein quality formation and yield improvement in bread wheat.