Thienoisoindigo-Based Conjugated Polymers Synthesized by Direct Arylation Polycondensation.

A series of thienoisoindigo (TIG)-based conjugated polymers (CPs) with high molecular weights are synthesized by direct arylation polycondensation (DArP) by using TIG derivatives as CBr monomer and multi-halogenated thiophene derivatives, i.e., (E)-1,2-bis(3,4-difluorothien-2-yl)ethene (4FTVT), (E)-1,2-bis(3,4-dichlorothien-2-yl)ethene (4ClTVT), 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT), and 3,3',4,4'-tetrachloro-2,2'-bithiophene (4ClBT), as CH monomers. Density functional theory (DFT) calculations reveal the high selectivity between α-CH bonds in 4FTVT, 4ClTVT, 4FBT, and 4ClBT and ß-CH bonds in TIG CBr monomer. All four resulting CPs exhibit low optical bandgaps of ca. 1.20 eV and ambipolar transport characteristics with both electron and hole mobility above 0.1 cm2  V-1  s-1 as elaborated with organic thin-film transistors (OTFTs). The polymer TIG-4FTVT delivers the best device performance. With this polymer, n-channel OTFTs with electron mobility up to 1.67 cm2  V-1  s-1 and p-channel OTFTs with hole mobility up to 0.62 cm2  V-1  s-1 are fabricated by modifying source/drain electrodes with polyethylenimine ethoxylated (PEIE) and MoO3 , respectively, to selectively inject electrons and holes.

FL118: A potential bladder cancer therapeutic compound targeting H2A.X identified through library screening.

The treatment of bladder cancer is limited by low drug efficacy and drug resistance. Hence, this study aimed to screen and identify potential drug precursors and investigate their mechanism of action. A set of camptothecin derivatives showing high anti-tumor potential was selected from early-stage research or literature and synthesized to construct a compound library. A total of 135 compounds were screened in T24 and J82 cells, revealing that FL118 significantly inhibited the proliferation of GC (gemcitabine + cisplatin)-sensitive/insensitive cells. FL118 exhibited excellent penetration and killing ability in organoids and three GC-insensitive patient-derived xenografts. Chemical proteomic and docking calculations were employed to identify binding proteins, indicating that FL118 can bind into H2A.X and its entwined DNA. The results of Cellular thermal shift assay and surface plasmon resonance (Kd = 3.77E-6) support the above findings. Fluorescence localization revealed widespread binding of FL118 within the cell nucleus. Furthermore, WB showed that FL118 increased cellular DNA damage, resulting in significant cell cycle inhibition. The binding of FL118 to H2A.X hindered the damage repair process, leading to apoptosis. Controllable adverse reactions were observed in mice treated with FL118. In conclusion, FL118 may be a superior anti-bladder cancer compound that acts as a molecular glue binding to both H2A.X and DNA. The resistance mediated by the DNA damage repair to DNA damage caused by GC regimen can be reversed by FL118. This distinct mechanism of FL118 has the potential to complement existing mainstream treatment approaches for bladder cancer.

An n-Type Conjugated Polymer with Low Crystallinity for High-Performance Organic Thermoelectrics.

Conjugated polymers (CPs) with low crystallinity are promising candidates for application in organic thermoelectrics (OTEs), particularly in flexible devices, because the disordered structures of these CPs can effectively accommodate dopants and ensure robust resistance to bending. However, n-doped CPs usually exhibit poor thermoelectric performance, which hinders the development of high-performance thermoelectric generators. Herein, we report an n-type CP (ThDPP-CNBTz) comprising two acceptor units: a thiophene-flanked diketopyrrolopyrrole and a cyano-functionalized benzothiadiazole. ThDPP-CNBTz shows a low LUMO energy level of below -4.20 eV and features low crystallinity, enabling high doping efficiency. Moreover, the dual-acceptor design enhances polaron delocalization, resulting in good thermoelectric performance. After n-doping, ThDPP-CNBTz exhibits an average electrical conductivity (σ) of 50.6 S cm-1 and a maximum power factor (PF) of 126.8 µW m-1 K-2, which is among the highest values reported for solution-processed n-type CPs to date. Additionally, a solution-processed flexible OTE device based on doped ThDPP-CNBTz exhibits a maximum PF of 70 µW m-1 K-2; the flexible device also shows remarkable resistance to bending strain, with only a marginal change in σ after 600 bending cycles. The findings presented in this work will advance the development of n-type CPs for OTE devices, and flexible devices in particular.

Conjugated Polymers from Direct Arylation Polycondensation of 3,4-Difluorothiophene-Substituted Aryls: Synthesis and Properties.

3,4-Difluorothiophene-substituted aryls, i.e., 1,4-bis(3,4-difluorothiophen-2-yl)-benzene (Ph-2FTh), 1,4-bis(3,4-difluorothiophen-2-yl)-2,5-difluorobenzene (2FPh-2FTh), and 4,7-bis(3,4-difluorothiophen-2-yl)-2,1,3-benzothiadiazole (BTz-2FTh), are synthesized as C─H monomers for the synthesis of conjugated polymers (CPs) via direct arylation polycondensation (DArP) with diketopyrrolopyrrole (DPP) and isoindigo (IID) derivatives as C─Br monomers. The Gibbs free energies of activation for direct arylation (ΔG298 K , kcal mol-1 ) for α─C─H bonds of thiophene moieties as calculated by density functional theory (DFT) are 14.3, 16.5, and 16.4 kcal mol-1 for Ph-2FTh, 2FPh-2FTh and BTz-2FTh, respectively, meaning that inserting an electron-deficient unit in 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT, ΔG298K : 14.6 kcal mol-1 ) may cause a reactivity decrease of the C─H monomers. Photophysical and semiconducting properties of the resulting six CPs (i.e., DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz) are characterized in detail. DPP-based CPs show ambipolar transport properties while IID-based ones exhibited n-type behavior owing to the deeper frontier molecular orbital energy levels of IID-based CPs. With source/drain electrodes modified with polyethylenimine ethoxylated, n-channel organic thin-film transistors with maximum electron mobility of 0.40, 0.54, 0.29, 0.05, 0.16, and 0.01 cm2 V-1 s-1 for DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz, respectively, are fabricated. DPP-2FPh exhibits the best device performance due to the good film morphology and the highest intermolecular packing order.

Efficient Biosynthesis of Acidic/Lactonic Sophorolipids and Their Application in the Remediation of Cyanobacterial Harmful Algal Blooms.

Cyanobacterial harmful algal blooms (CyanoHABs) pose significant threats to human health and natural ecosystems worldwide, primarily caused by water eutrophication, increased surface water temperature, and co-occurring microorganisms. Urgent action is needed to develop an eco-friendly solution to effectively curb the proliferation of CyanoHABs. Sophorolipids (SLs) are fully biodegradable biosurfactants synthesized by Starmerella bombicola. They can be classified into lactone and acid types. The lactone type displays strong antimicrobial activity, while the acid type exhibits good solubility, which make them ideal agents for mitigating CyanoHABs. Nevertheless, the broad utilization of SLs are hindered by their expensive production costs and the absence of effective genetic editing tools in the native host. In this study, we constructed recombinant strains capable of producing either acidic or lactonic SLs using the CRISPR-Cas9 gene editing system. The yields of acidic and lactonic SLs reached 53.64 g/L and 45.32 g/L in a shaking flask, respectively. In a 5 L fermenter, acidic SLs reached 129.7 g/L using low-cost glucose and rapeseed oil as substrates. The addition of 5 mg/L lactonic SLs effectively degraded cyanobacteria within 30 min, and a ratio of 8.25:1.75 of lactonic to acidic SLs showed the highest degradation efficiency. This study offers a safe and promising solution for CyanoHABs treatment.

A High-Performance n-Type Thermoelectric Polymer from C-H/C-H Oxidative Direct Arylation Polycondensation.

n-Type conjugated polymers (CPs) are crucial in the applications of organic electronics. Direct coupling of electron-deficient C-H monomer via selective C-H activation, namely C-H/C-H oxidative direct arylation polycondensation (Oxi-DArP), is an ideal approach toward such CPs. Herein, Oxi-DArP is firstly adopted to synthesize a high-performance n-type CP using a newly developed monomer, i.e., 3,6-di(thiazol-5-yl)-diketopyrrolopyrrole (Tz-5-DPP). Tz-5-DPP based homopolymer PTz-5-DPP with a molecular weight of 22 kDa has been synthesized via Oxi-DArP. After n-doping, PTz-5-DPP films exhibited electric conductivity values up to 8 S cm-1 and power factors (PFs) up to 106 µW m-1 K-2 . Notably, this PF value is the highest for n-type polymer thermoelectric materials to date. The Oxi-DArP synthesis and the excellent n-type performance of the polymer make this work an important step toward the straightforward and sustainable preparation of high-performance n-type polymer semiconductors.

eIF5B regulates the expression of PD-L1 in prostate cancer cells by interacting with Wig1.

BACKGROUND: Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study. METHODS: In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR (qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo. RESULTS: Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells. CONCLUSION: eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.

Altered staining patterns and expression level of Engrailed-2 in benign prostatic hyperplasia and prostate Cancer predict prostatic disease progression.

BACKGROUND: Prostate cancer (PC), a common malignant tumor, is the second-leading cause of cancer death among American men. Its successful treatment greatly relies on the early diagnose. Engrailed-2 (EN2) has been confirmed being existed with a high level in the urine of PC patients. In this study, to explore the application of EN2 in PC, we detected the immunohistochemical staining difference and EN2 expression level between benign prostatic hyperplasia (BPH) and PC. METHODS: We developed a monoclonal antibody against the helix 3 in EN2 and confirmed its specificity with Western blotting (WB) and immunofluorescence detecting the subcellular localization of endogenous and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145). We conducted immunohistochemical staining using this homemade antibody, and RT-PCR to detect the expression of EN2 in 25 PC and 25 BPH cases, and analyzed the correlation of EN2 expression and PC clinical staging. RESULTS: The results of WB and immunofluorescence showed our homemade EN2 monoclonal antibody could specifically bind endogenous and exogenous EN2 protein in three different PC cell lines. Endogenous EN2 was generally expressed in the cytoplasm and exogenous EN2 mostly existed in the nucleus of these cell lines. Immunohistochemical staining in PC had extremely stronger signals than that in BPH, suggesting a higher EN2 expression level in PC, which was confirmed by RT-PCR. Interestingly, the stained areas in BPH tissues were mainly in nucleus and cytoplasm, while in PC tissues were mainly on cytomembrane. Moreover, the expression level of EN2 was positively correlated with the PC clinical staging. CONCLUSION: Using our homemade EN2 antibody, we have found different staining patterns and expression level of EN2 in BPH and PC,which may be helpful to predict prostatic disease progression.

Publication Trends and Research Hotspots of the Cardiorenal Syndrome: A Bibliometrics and Visual Analysis from 2003 to 2023.

INTRODUCTION: Cardiorenal syndrome encompasses a range of disorders involving both the heart and kidneys, wherein dysfunction in one organ may induce dysfunction in the other, either acutely or chronically. METHODS: This study conducted a literature search on cardiorenal syndrome from January 1, 2003, to September 8, 2023. Meanwhile, a quantitative analysis of the developmental trajectory, research hotspots and evolutionary trends in the field of cardiorenal syndrome through bibliometric analysis and knowledge mapping was carried out. RESULTS: The annual publication trend analysis revealed a consistent annual increase in cardiorenal syndrome literature over the last 20 years. The IL6, REN, and INS genes were identified as the current research hotspots. CONCLUSION: The field of cardiorenal syndrome exhibits promising potential to grow and is emerging as a prominent research area. Future endeavours should prioritise a comprehensive understanding of the field and foster multi-centre co-operation among different countries and regions.

Mapping global research landscape and trend of nano-drug delivery system for urological cancers: a bibliometric analysis.

Aim: We conducted a bibliometric analysis to quantitatively study the development pathway, research hotspots and evolutionary trends of nano-drug delivery systems (NDDS) in treating urological tumors.Materials & methods: We used the Web of Science Core Collection to retrieve the literature related to NDDS in the urological tumors up to November 1, 2023. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer and R-Bibliometrix. The major aspects of analysis included contributions from different countries/regions, authors' contributions, keywords identification, citation frequencies and overall research trends.Results: We included 3,220 articles. The analysis of annual publication trends revealed significant growth in this field since 2010, which has continued to the present day. The United States and China have far exceeded other countries/regions in the publication volume of papers in this field. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Mucoadhesive NDDS for intravesical drug delivery is a hotspot and a potential research material for bladder cancer.Conclusion: The field of NDDS in urological tumors has emerged as a research hotspot. Future research should focus on synergistic effects of NDDS with other treatment modalities.

[Box: see text].

Social appearance anxiety among the dark tetrad and self-concealment.

This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.

Network pharmacology and molecular docking reveal potential mechanisms of ginseng in the treatment of diabetes mellitus-induced erectile dysfunction and asthenospermia.

Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.

Metabolic Engineering of Candida tropicalis for the De Novo Synthesis of ß-Ionone.

ß-ionone, a norisoprenoid, is a natural aromatic compound derived from plants, which displays various biological activities including anticancer, antioxidant and deworming properties. Due to its large biomass and strong environmental tolerance, the nonconventional oleaginous yeast Candida tropicalis was selected to efficiently synthesize ß-ionone. We initially investigated the capacity of the cytoplasm and subcellular compartments to synthesize ß-ionone independently. Subsequently, through adaptive screening of enzymes, functional identification of subcellular localization signal peptides and subcellular compartment combination strategies, a titer of 152.4 mg/L of ß-ionone was achieved. Finally, directed evolution of rate-limiting enzyme and overexpression of key enzymes were performed to enhance ß-ionone production. The resulting titer was 400.5 mg/L in shake flasks and 730 mg/L in a bioreactor. This study demonstrates the first de novo synthesis of ß-ionone in C. tropicalis, providing a novel cellular chassis for terpenoid fragrances with considerable industrial potential.

Effect of smoking on the recurrence and progression of non-muscle-invasive bladder cancer.

BACKGROUND: It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue. OBJECTIVE: To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients. METHODS: A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research. RESULTS: A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients. CONCLUSIONS: Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.

Characterization and determination of holin protein of Streptococcus suis bacteriophage SMP in heterologous host.

BACKGROUND: Holins are a group of phage-encoded membrane proteins that control access of phage-encoded endolysins to the peptidoglycan, and thereby trigger the lysis process at a precise time point as the 'lysis clock'. SMP is an isolated and characterized Streptococcus suis lytic phage. The aims of this study were to determine the holin gene, HolSMP, in the genome of SMP, and characterized the function of holin, HolSMP, in phage infection. RESULTS: HolSMP was predicted to encode a small membrane protein with three hydrophobic transmembrane helices. During SMP infections, HolSMP was transcribed as a late gene and HolSMP accumulated harmlessly in the cell membrane before host cell lysis. Expression of HolSMP in Escherichia coli induced an increase in cytoplasmic membrane permeability, an inhibition of host cell growth and significant cell lysis in the presence of LySMP, the endolysin of phage SMP. HolSMP was prematurely triggered by the addition of energy poison to the medium. HolSMP complemented the defective λ S allele in a non-suppressing Escherichia coli strain to produce phage plaques. CONCLUSIONS: Our results suggest that HolSMP is the holin protein of phage SMP and a two-step lysis system exists in SMP.

Combined antibacterial activity of phage lytic proteins holin and lysin from Streptococcus suis bacteriophage SMP.

Development of novel antibacterial agents is required to control infection with multidrug-resistant Streptococcus suis. HolSMP and LySMP, the holin and lysin of S. suis serotype 2 bacteriophage, named SMP, are responsible for lysis of host cells and release of progeny phage. HolSMP and LySMP expressed in Escherichia coli BL21(DE3) exerted efficient activity at 37 °C, pH 5.2, with addition of 0.8 % ß-mercaptoethanol. Lytic spectra of purified HolSMP, LySMP or HolSMP + LySMP mixture were investigated. HolSMP, exhibiting a narrow lytic spectrum, was effective against Staphylococcus aureus and Bacillus subtilis, which were insensitive to LySMP. Moreover, HolSMP was identified as a promising antibacterial agent which was able to extend the spectrum of LySMP. The data suggest that combined use of holin and lysin could be a candidate strategy for resolution of drug resistance.

[Current advance in the topological structure and function of holin encoded by bacteriophage lambda--a review].

The holin-lysin two-step lysis system widely exists in double stranded DNA bacteriophages for the release of progeny bacteriophage from an infected bacterial cell at the final stage of phage infection. Lambda bacteriophage is a prototype for studying holin. The S gene in Lambda bacteriophage has a dual-start motif and encodes holin S105 and antiholin S107. Here, we reviewed the progress in topological structure of holin from Lambda bacteriophage and its formation of membrane lethal holes. We also discussed the potential of the holin in the control of bacterial infection.

A CRISPR-Cas9 System-Mediated Genetic Disruption and Multi-fragment Assembly in Starmerella bombicola.

Gene editing technology plays an extremely significant role in synthetic biology and metabolic engineering. Traditional genetic manipulation methods, such as homologous recombination, however, are inefficient, time-consuming, and barely feasible when disrupting multiple genes simultaneously. Starmerella bombicola, a nonconventional yeast that overproduces sophorolipids, lacks convenient genetic tools for engineering strains. Here, we developed an efficient CRISPR-Cas9 genome editing technology by combining molecular element mining and expression system optimization for S. bombicola. This CRISPR-Cas9 system improved the efficiency of gene-integration/target gene-introducing disruption by homology-directed repair and realized the multi-gene simultaneous disruptions. Based on this CRISPR-Cas9 system, we also further constructed an engineered strain via the in vivo assembly of multiple DNA fragments (10 kb) that can produce acid-type sophorolipids. These results showed that the CRISPR-Cas9 system may be an efficient and convenient strategy to perform genetic manipulation in S. bombicola.

Struggling or Liberating? The Effects of Machiavellianism on Break-Up Distress.

Negative emotions caused by break-up are the key work of university students' psychological intervention. It is important to explore the specific factors of break-up distress for university students' psychological intervention. Therefore, we investigated 869 university students to examine the effect of Machiavellianism and psychological capital on break-up distress, as well as its gender difference. The results indicated that high Machiavellians experience more break-up distress. Moreover, through structural equation models, we found that as for female university students, psychological capital mediated the relationship between Machiavellianism and break-up distress. However, as for male university students, the mediation effect was not significant. It means that for female university students, psychological capital acted as the mechanism to connect Machiavellianism and break-up distress.