Molecular Strategies Research Articles

Strategic Design of Anion-Responsive Triarylboranes Exhibiting Colorimetric and Fluorometric Red-Shift for Sensing and Optoelectronic Applications.

Triarylboranes (TABs) have been employed as colorimetric and/or fluorometric anion sensors. The majority of TAB-based anion sensors exhibit blue-shift modes of absorption and photoluminescence (PL) or turn off of PL, attributed to the intrinsic electronic polarity of the trivalent boron unit in their molecular designs. In this Concept article, we introduce a novel approach to modulating the photophysical properties of TABs toward a red-shift mode by balancing the dual, opposing roles of the amine-bridged TAB (phenazaborine). This molecular design strategy enables significant changes in color and emission response to anions, shifting to the lower energy regime in solution. Additionally, this approach is applicable to the solid-state modulation of PL in films and organic light-emitting diodes (OLEDs).

NAT10 functions as a pivotal regulator in gastric cancer metastasis and tumor immunity.

Gastric cancer (GC) presents a significant global health burden, with metastasis being the leading cause of treatment failure and mortality. NAT10, a regulatory protein involved in mRNA acetylation, has been implicated in various cancers. However, its role in GC, especially concerning metastasis and immune interactions, remains unclear. Utilizing multi-omics data from gastric cancer samples, we conducted comprehensive analyses to investigate NAT10 expression, its correlation with clinical parameters and immune relevance. Bioinformatics analysis and digital image processing were employed for this purpose. Furthermore, in vitro and in vivo experiments were conducted to elucidate the functional role of NAT10 in gastric cancer progression, aiming to provide deeper biological insights. Our findings reveal a significant association between NAT10 expression and various aspects of transcriptional, protein, as well as tumor immunity in GC patients. Additionally, we demonstrated that NAT10 promotes gastric cancer cell proliferation and migration, both in cellular models and in animal studies, suggesting its involvement in early tumor microvascular metastasis. NAT10 emerges as a promising molecular target, offering potential avenues for further research into molecular mechanisms and therapeutic strategies for GC.

Energy conversion and transport in molecular-scale junctions

Molecular-scale junctions (MSJs) have been considered the ideal testbed for probing physical and chemical processes at the molecular scale. Due to nanometric confinement, charge and energy transport in MSJs are governed by quantum mechanically dictated energy profiles, which can be tuned chemically or physically with atomic precision, offering rich possibilities beyond conventional semiconductor devices. While charge transport in MSJs has been extensively studied over the past two decades, understanding energy conversion and transport in MSJs has only become experimentally attainable in recent years. As demonstrated recently, by tuning the quantum interplay between the electrodes, the molecular core, and the contact interfaces, energy processes can be manipulated to achieve desired functionalities, opening new avenues for molecular electronics, energy harvesting, and sensing applications. This Review provides a comprehensive overview and critical analysis of various forms of energy conversion and transport processes in MSJs and their associated applications. We elaborate on energy-related processes mediated by the interaction between the core molecular structure in MSJs and different external stimuli, such as light, heat, electric field, magnetic field, force, and other environmental cues. Key topics covered include photovoltaics, electroluminescence, thermoelectricity, heat conduction, catalysis, spin-mediated phenomena, and vibrational effects. The review concludes with a discussion of existing challenges and future opportunities, aiming to facilitate in-depth future investigation of promising experimental platforms, molecular design principles, control strategies, and new application scenarios.

Telomere-to-telomere Genome Assembly of two representative Asian and European pear cultivars

As the third most important temperate fruit, Pear (Pyrus spp.) exhibits a remarkable genetic diversity and is classified into two mainly categories known as Asian pear and European pear. Although several pear genomes are available, most of the released versions are fragmented and not chromosome-level high-quality. In this study, we report two high-quality genomes for Pyrus bretschneideri Rhed. cv. ‘Danshansuli’ (DS) and Pyrus communis L. cv. ‘Conference’ (KFL), which represent the predominant Asian and European cultivars, respectively, with nearly telomere-to-telomere (T2T) gap-free level. The finally assembled genome sizes for DS and KFL were 510.98 Mb and 510.71 Mb, respectively, with Contig N50 of 29.47 Mb and 30.47 Mb, where each chromosome was represented by a single contig. The DS and KFL genomes yielded a total of 46,394 and 44,702 protein-coding genes, respectively. Among these genes, the functional annotation accounted for 96.47% and 96.46% in the DS and KFL genomes. The two novels nearly T2T genomic information offers an invaluable resource for comparative genomics, genetic diversity analysis, molecular breeding strategies, and functional exploration.

Theoretical exploration of energetic molecular design strategy: functionalization of C or N and structural selection of imidazole or pyrazole.

In researching energetic materials with high energy density, it is an effective method to introduce explosophoric groups. In this study, four series of energetic compounds were designed by functionalizing with C- or N-, introducing energetic groups -CH(NO2)2, -CF(NO2)2, -C(NO2)2(NF2), -C(NO2)3, and-CH(NF2)2 into imidazole and pyrazole structures. Density functional theory was employed to optimize the structure of the target compound and subsequently to predict and evaluate its performance based on this. Meanwhile, the sensitivity of the compounds was predicted based on their electrostatic potential analysis. Following analysis of the geometric structure, detonation performance, and sensitivity of the compounds, three factors were discussed: energetic groups, functionalization methods, and skeleton structure differences. The results indicate that C-functionalization has advantages only in density, but N-functionalization is better in thermal stability, heat of formation, and sensitivity. Meanwhile, the data shows that imidazole-based compounds exhibited greater density and detonation performance in the target compounds designed within this study, while pyrazoles have a higher heat of formation and chemical stability. By analyzing the design strategy of C- or N-functionalization of novel high-energy groups on energetic imidazole or pyrazole rings and selecting a more suitable molecular construction strategy, this study provides a theoretical approach for the development of new energetic materials with excellent performance. Gaussian 09 and Multiwfn 3.8 packages are the software used for calculation, and the electrostatic potentials were depicted using the VMD program. In this study, the imidazole and pyrazole derivatives were optimized at the B3PW91/6-311G (d, p) level to acquire the relevant data for the compounds.

Non‐Fluorinated Cyclic Ether‐Based Electrolyte with Quasi‐Conjugate Effect for High‐Performance Lithium Metal Batteries

AbstractFluorinated ether‐based electrolytes are commonly employed in lithium metal batteries (LMBs) to attenuate the coordination ability of ether solvents with Li+ and induce inorganic‐rich interphase, whereas fluorination inevitably introduces exorbitant production expenses and environmental anxieties. Herein, a non‐fluorinated molecular design strategy has been conceptualized by incorporating methoxy as an electron‐donating group to generate a quasi‐conjugate effect for tuning the affinity of Li+‐solvent, thereby enabling the cyclic ether solvent 2‐methoxy‐1,3‐dioxolane with weak solvation ability and exceptional Li metal‐compatibility. Accordingly, the optimized electrolyte exhibits anion‐dominant solvation structure for inorganic‐rich interphase and fulfills an impressive Li plating/stripping Coulombic efficiency of 99.6 %. As‐fabricated Li||LiFePO4 full cells with limited Li (N/P=2.5) showcase a high capacity retention of 83 % after 150 cycles, indicating excellent cycling stability. Moreover, the full LMBs demonstrate exceptional tolerance towards a wide temperature range from −20 °C to 60 °C, displaying a remarkable capacity retention of 90 % after 110 cycles at −20 °C. Such a molecular design strategy offers a promising avenue for electrolyte engineering beyond fluorination in order to cultivate high‐performance LMBs.

ITRAQ-Based Proteomic Analysis Unveils NCAM1 as a Novel Regulator in Doxorubicin-Induced Cardiotoxicity and DT-010-Exerted Cardioprotection

Background: Doxorubicin (DOX) causes lethal cardiotoxicity, which limits its clinical utility. The molecular mechanisms and effective strategies to combat its cardiotoxicity need further exploration. DT-010, a novel conjugate of danshensu (DSS) and tetramethylpyrazine( TMP), is considered a promising candidate for treating DOX-induced cardiotoxicity. In this study, we aimed to investigate the underlying molecular mechanisms of DOX-induced cardiotoxicity and the cardioprotective effects of DT-010. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) in proteomics analysis was employed to analyze the differentially expressed proteins in DOX-injuried hearts. Gene ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to evaluated the potential mechanisms of DOXinduced cardiotoxicity. The effects of NCAM1 on DOX-induced cardiotoxicity in H9c2 cells, as well as the cardioprotection of DT-010 were assessed through NACM1siRNA transfection, cell viability assay, cell apoptosis staining, reactive oxygen species measurement, and western blotting. Results: Proteomics analysis revealed that several signaling pathways, including the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, were involved in DOX-induced cardiotoxicity. NCAM1 is one of the significantly changed proteins. DT-010 treatment regulated NCAM1 protein expression. Silencing NCAM1 in DOX-treated H9c2 cells decreased cell viability, increased cell apoptosis and reactive oxygen species (ROS) generation, and attenuated the cardioprotective effects of DT-010. Furthermore, NCAM1 knockdown promoted p38 activation and inhibited the expressions of peroxisome proliferator-activated receptor gamma coactivator- 1 alpha (PGC-1α) and heme oxygenase-1 (HO-1) in DOX-treated cells. Conclusion: These findings indicate a definite role of NCAM1 in DOX-induced cardiotoxicity and DT-010-exerted cardioprotection, which is mediated through the p38 and Sirt1/PGC- 1α/HO-1 pathway.

A Review of Antimicrobial Peptides: Structure, Mechanism of Action, and Molecular Optimization Strategies

Antimicrobial peptides (AMPs) are bioactive macromolecules that exhibit antibacterial, antiviral, and immunomodulatory functions. They come from a wide range of sources and are found in all forms of life, from bacteria to plants, vertebrates, and invertebrates, and play an important role in controlling the spread of pathogens, promoting wound healing and treating tumors. Consequently, AMPs have emerged as promising alternatives to next-generation antibiotics. With advancements in systems biology and synthetic biology technologies, it has become possible to synthesize AMPs artificially. We can better understand their functional activities for further modification and development by investigating the mechanism of action underlying their antimicrobial properties. This review focuses on the structural aspects of AMPs while highlighting their significance for biological activity. Furthermore, it elucidates the membrane targeting mechanism and intracellular targets of these peptides while summarizing molecular modification approaches aimed at enhancing their antibacterial efficacy. Finally, this article outlines future challenges in the functional development of AMPs along with proposed strategies to overcome them.

The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy

BackgroundBacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity.ResultsWe could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores.EJt4aqYa_PFzdC4ihACHg3Video ConclusionsThese findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

Robust Sandwich‐Structured Thermally Activated Delayed Fluorescence Molecules Utilizing 11,12‐Dihydroindolo[2,3‐a]carbazole as Bridge

AbstractConstructing folded molecular structures is emerging as a promising strategy to develop efficient thermally activated delayed fluorescence (TADF) materials. Most folded TADF materials have V‐shaped configurations formed by donors and acceptors linked on carbazole or fluorene bridges. In this work, a facile molecular design strategy is proposed for exploring sandwich‐structured molecules, and a series of novel and robust TADF materials with regular U‐shaped sandwich conformations are constructed by using 11,12‐dihydroindolo[2,3‐a]carbazole as bridge, xanthone as acceptor, and dibenzothiophene, dibenzofuran, 9‐phenylcarbazole and indolo[3,2,1‐JK]carbazole as donors. They hold outstanding thermal stability with ultrahigh decomposition temperatures (556–563 °C), and exhibit fast delayed fluorescence and excellent photoluminescence quantum efficiencies (86 %–97 %). The regular and close stacking of acceptor and donors results in rigidified molecular structures with efficient through‐space interaction, which are conducive to suppressing intramolecular motion and reducing reorganized excited‐state energy. The organic light‐emitting diodes (OLEDs) using them as emitters exhibit excellent electroluminescence performances, with maximum external quantum efficiencies of up to 30.6 %, which is a leading value for the OLEDs based on folded TADF emitters. These results demonstrate the proposed strategy of employing 11,12‐dihydroindolo[2,3‐a]carbazole as bridge for planar donors and acceptors to construct efficient folded TADF materials is applicable.

Robust self-healing capacity and high mechanical properties of castor oil-based waterborne polyurethane based on “kill two birds with one stone” strategy

Achieving ideal combination of high self-healing efficiency and good mechanical properties is of significance for the breakthrough in the application of self-healing materials. Herein, the functionalized castor oil-based waterborne polyurethane (DA-CWPU) was constructed based on “killing two birds with one stone” molecular design strategy with the addition of self-healing monomer D-A adduct. Firstly, D-A adduct containing flexible D-A bonds and rigid ring structure was prepared by D-A reaction with furfuryl alcohol (FA) and bismaleimide (BMI) as raw materials, which could not only effectively enhanced the self-healing ability of the material, but also ensured the strong mechanical properties. Then, DA-CWPU emulsion with favourable self-healing and mechanical properties was synthesized by the polymerization of castor oil (CO), isophorone diisocyanate (IPDI) and D-A adduct. The DA-CWPU film has preferable self-healing efficiency (93 % at 100 °C for 50 min), unique shape memory effect (rehabilitate after heating at 100 °C for 45 s), good toughness (485 MJ/m3), strong tensile strength (5.96 MPa) and sufficient elongation (115 %). At the same time, the self-healing DA-CWPU film can be recycled through solution casting. The sustainable castor oil-based waterborne polyurethane can be used as finishing agents for leather products, which realizes repeatedly self-healing in case of surface damage, greatly increasing the service life of the material and mechanical properties, providing a new approach for the development of mechanically robust self-healing materials.

Advances in Molecular Photoswitches: From Azobenzenes to Azoquinolines

Molecular photoswitches represent a dynamic and ever-growing research area based on the ability of molecules to convert (switch) between cis- (Z) and trans- (E) isomers. Azobenzenes are the most popular and widely employed Z-E photoswitchable molecules in the development of photoresponsive, multifunctional smart materials for various applications. The promising avenues in this field include molecular fine-tuning of azobenzene- based photoswitches and the creation of single or dual-functional probes. This short overview highlights recent advances in the design of molecular photoswitches, particularly the molecular design strategies of azobenzene-based photoswitches with their structural and electronic features. Particular attention is paid to azoquinolines, which seem to be a promising alternative to azobenzenes in the design of novel multifunctional photoswitches with improved photochromic properties. Here, we have also developed the novel star-shaped multiazoquinoline photoswitch comprising individual azoquinoline-based photochromes connected to a central trisubstituted 1,3,5-triformylphloroglucinol core by quantum chemical calculations. This unique structure is favorable for independent Z-E isomerization of each azoquinoline-based photochrome within one macromolecule.

Phosphorescent cyclometalated Ir(III) complexes with fluoranthene unit and their near-infrared (NIR) OLEDs showing NIR% higher than 99 %

With the aim to design and synthesize cyclometalated Ir(III) complexes with near-infrared (NIR) emission, a series of ppy-type ligands with fluoranthene unit have been synthesized bearing different aromatic nitrogen heterocycles of isoquinoline, quinoline, pyridine and benzo [d]thiazole. With these organic ligands, four [Ir (ppy)2 (acac)] complexes are prepared named as IrFTIQ, IrFTQL, IrFTPY and IrFTBZ. In solution, IrFTIQ can emit NIR phosphorescence at 738 nm, while IrFTQL (ca. 692 nm), IrFTPY (ca. 670 nm) and IrFTBZ (ca. 690 nm) are typical deep-red emitters. It should be noted that all these fluoranthene-based cyclometalated Ir(III) complexes show good electrochemical stability indicated by their reversible redox procedures. When doped in the emission layer of OLEDs, IrFTIQ and IrFTBZ can furnish NIR electroluminescence (EL) at 748 nm and 700 nm, respectively, while the devices with IrFTPY as emitter can furnish deep-red EL. Critically, the optimized OLED doped with IrFTIQ can achieve maximum external quantum efficiency (EQE) as high as 5.01 % and a radiance up to 6284 mW Sr−1 m−2. Critically, the NIR OLEDs based on IrFTIQ can furnish EL with NIR component (NIR%) of a total spectrum > 99 %. All these encouraging results definitely demonstrate the effectiveness of our molecular design strategy for the new-type Ir(III) NIR phosphorescent complexes and the great potential of the fluoranthene group in developing high-performance Ir-based NIR phosphors for OLEDs.

Understanding the Nonradiative Charge Recombination in Organic Photovoltaics: From Molecule to Device

AbstractOrganic photovoltaics (OPVs) have made significant strides with efficiencies now exceeding 20%, positioning them as potential competitors to inorganic solar technologies. One of the most critical challenges toward this goal is the severe open‐circuit voltage (Voc) loss caused by the nonradiative charge recombination (NRCR). Herein, this review comprehensively summarizes the NRCR mechanisms and suppression techniques of OPVs across various scales from molecule to device. Specifically, the origins of NRCR in a single molecule are first summarized, and molecular design principles toward high photoluminescence quantum yield are reviewed following the Marcus theory. Next, the effect of aggregation on NRCR is reviewed, as well as the molecular and processing strategies to modulate the film packing for NRCR suppression. Furthermore, the progresses in the avoidance of nonradiative loss pathways mediated by charge transfer states and triplet states in donor:acceptor bulk heterojunctions are tracked. Besides, the interfacial optimization and device structure design to maximize the electroluminescent quantum efficiency are presented. Finally, several potential pathways toward curtailing NRCR for high‐performance OPVs are outlined. Therefore, this review shows an insightful perspective to understand and mitigate the NRCR at multi‐scales, and is poised to provide a clear roadmap for the next breakthrough of OPVs.

The underrepresented quinolinone alkaloids in genera Penicillium and Aspergillus: structure, biology, and biosynthetic machinery.

Quinolone alkaloids are N-heterocycles with extensive structural diversity, mainly derived from in fungi from anthranilic acid and amino acids as precursors with a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, and insecticidal activities. The quinolone basic skeleton comprised of either 2-quinolones or 4-quinolones generated more than one hundred compounds. Several reviews discussed quinolones; particularly, the fluoroquinolones, yet few studies tackled natural quinolones. Many of these quinolones were not assayed for their antimicrobial potential despite their unique stereospecificity, which can supersede synthetic quinolones if their discovery is coupled with OMICS techniques, biochemical and molecular strategies as heterologous expression to maximize their yield. Herein, we conducted a comprehensive review of the quinolone's family in Aspergillus and Penicillium species, the exclusive producers of quinolones whether they are soil, endophytic or marine derived highlighting their isolation, chemical structures, pharmacological effects, structure activity relationships if any, and biosynthetic machinery. We believe that our initiative will pave the way for further development of natural quinolones as future antimicrobial agents.

A hot exciton organic glassy scintillator for high-resolution X-ray imaging.

Hot exciton organic scintillators offer promising prospects due to their efficient generation of bright triplet excitons and ultrafast response time, having potential applications in security detection and medical diagnostics. However, fabricating large-area, highly transparent scintillator screens still remains challenging, impeding the realization of high-resolution X-ray imaging. Herein, we firstly demonstrate a novel highly-transparent hot exciton organic glassy scintillator (>87% transmittance @ 450-800 nm), produced using a low-temperature melt-quenching method with 2',5'-difluoro-N4,N4,N4'',N4''-tetraphenyl-[1,1':4',1''-terphenyl]-4,4''-diamine (DTPA2F) powder. Remarkably, compared to crystalline DTPA2F, which has a photoluminescence quantum yield of 67.8% and a relative light yield of 46 400 ± 406 photons MeV-1, the DTPA2F glass retains 49.8% and 28 341 ± 246 photons MeV-1, respectively. This results in a low detection limit of about 53.7 nGy s-1 and an ultrafast decay time of 1.66 ns for DTPA2F glass. Besides, it exhibits excellent environmental stability with no recrystallization or degradation after over 100 days of exposure to ambient conditions. Furthermore, the scintillator screen demonstrates exceptional spatial resolution of 38.5 lp mm-1 for X-ray imaging. It provides a simple molecular design strategy and a screen fabrication method for developing large-area, highly-transparent, efficient and ultrafast organic glassy scintillators.

Bioinspired Molecular Scalpel for Two-Dimensional Metal-Organic Nanosheet: Design Strategies and Recent Progress.

Ultrathin two-dimensional (2D) metal-organic nanosheets (MONs) have attracted continued attention in the field of advanced functional materials. Their nanoscale thickness, high surface-to-volume ratio, and abundant accessible active sites, are superior advantages compared with their 3D bulk counterparts. Bioinspired molecular scalpel strategy is a promising method for the creation of 2D MONs, and may solve the current shortcomings of MONs synthesis. This review aims to provide a state-of-the-art overview of molecular scalpel strategies and share the results of current development to provide a better solution for MONs synthesis. Different types of molecular scalpel strategies have been systematically summarized. Both mechanisms, advantages and limitations of multiform molecular scalpel strategies have been discussed. Besides, the challenges to be overcome and the question to be solved are also introduced.

Controlling (E/Z)-Stereoselectivity of -NHC=O Chlorination: Mechanism Principles for Wide Scope Applications.

Organic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in the halo-ligand design. Straightforward (but expensive) catalyzed stereospecific halogenation has been reported. Historically, PCl5 served access to uncatalyzed stereoselective chlorination although the stereochemical outcomes were influenced by steric parameters. Nonetheless, stereochemical investigation of PCl5 reaction mechanism with carbamoyl (RCONHX) compounds has never been addressed. Herein, we provide the first comprehensive stereochemical mechanistic explanation outlining halogenation of carbamoyl compounds with PCl5; the key regioselectivity-limiting nitrilimine intermediate (8-Z.HCl); how substitution pattern influences regioselectivity; why oxadiazole byproduct (P1) is encountered; stereo-electronic factors influencing the hydrazonoyl chloride (P2) production; and discovery of two stereoselectivity-limiting parallel mechanisms (stepwise and concerted) of elimination of HCl and POCl3. DFT calculations, synthetic methodology optimization, X-ray evidence and experimental reaction kinetics study evidence all supported the suggested mechanism proposal (Scheme 2). Finally, we provide mechanism-inspired future recommendations for directing the reaction stereoselectivity toward elusive and stereochemically inaccessible (E)-bis-hydrazonoyl chlorides along with potentially pivotal applications of both (E/Z)-stereoisomers especially in medicinal chemistry and protein modification.

Multi-omics framework to reveal the molecular determinants of fermentation performance in wine yeast populations

BackgroundConnecting the composition and function of industrial microbiomes is a major aspiration in microbial biotechnology. Here, we address this question in wine fermentation, a model system where the diversity and functioning of fermenting yeast species are determinant of the flavor and quality of the resulting wines.ResultsFirst, we surveyed yeast communities associated with grape musts collected across wine appellations, revealing the importance of environmental (i.e., biogeography) and anthropic factors (i.e., farming system) in shaping community composition and structure. Then, we assayed the fermenting yeast communities in synthetic grape must under common winemaking conditions. The dominating yeast species defines the fermentation performance and metabolite profile of the resulting wines, and it is determined by the initial fungal community composition rather than the imposed fermentation conditions. Yeast dominance also had a more pronounced impact on wine meta-transcriptome than fermentation conditions. We unveiled yeast-specific transcriptomic profiles, leveraging different molecular functioning strategies in wine fermentation environments. We further studied the orthologs responsible for metabolite production, revealing modules associated with the dominance of specific yeast species. This emphasizes the unique contributions of yeast species to wine flavor, here summarized in an array of orthologs that defines the individual contribution of yeast species to wine ecosystem functioning.ConclusionsOur study bridges the gap between yeast community composition and wine metabolite production, providing insights to harness diverse yeast functionalities with the final aim to producing tailored high-quality wines.74dL8hDE5Rym1TqBfqxSSDVideo

Targeting esophageal carcinoma: molecular mechanisms and clinical studies.

Esophageal cancer (EC)is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.