Reactive Superhydrophobic Surfaces for Interlayer Electrical Connectivity in Three-dimensional Electronics.

This study describes the development of a new type of amine-reactive superhydrophobic (RSH) film that is facilely coated on various substrates using a single-step process, while the versatility of this RSH film offers a reliable solution for efficient formation of complex and robust interlayer electrical connectivity (IEC) in 3D electronic systems. The excellent spatial controllability of surface amine modification enables the generation of vertical circuits in situ, providing a distinct way to connect circuits located on different layers. Moreover, the inherent superhydrophobicity and porosity exhibit the required anti-fouling and breathability properties, making the RSH-based IEC well-suited for applications where exposure to environmental gas and liquid contaminants is likely. This approach provides another avenue towards the development of IEC in 3D flexible integrated electronics, opening up new possibilities for the advancement of this field.

The Buckling Spectra of Nanoparticle Surfactant Assemblies.

Fine control over the mechanical properties of thin sheets underpins transcytosis, cell shape, and morphogenesis. Applying these principles to artificial, liquid-based systems has led to reconfigurable materials for soft robotics, actuation, and chemical synthesis. However, progress is limited by a lack of synthetic two-dimensional membranes that exhibit tunable mechanical properties over a comparable range to that seen in nature. Here, we show that the bending modulus, B, of thin assemblies of nanoparticle surfactants (NPSs) at the oil-water interface can be varied continuously from sub-kBT to 106kBT, by varying the ligands and particles that comprise the NPS. We find extensive departure from continuum behavior, including enormous mechanical anisotropy and a power law relation between B and the buckling spectrum width. Our findings provide a platform for shape-changing liquid devices and motivate new theories for the description of thin-film wrinkling.

The Association Between Admission Anemia and Poststroke Depression.

ABSTRACT: Poststroke depression (PSD) is the most frequent and important neuropsychiatric problem afflicting these patients. Anemia is common in many of these individuals presenting with acute stroke. This study determined whether there is a relationship between anemia on hospital admission and PSD. Two hundred eighty-four acute stroke patients were included in the study. Among them, there were 88 PSD patients, whereas another 196 were non-PSD patients. Clinical depression symptoms were diagnosed according to DSM-4 (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria and a HAMD-17 (the 17-item Hamilton Depression Scale) score ≥8 at 1 month after stroke. In the PSD patients, 27.3% of them presented with anemia, whereas only 12.8% of the non-PSD patients had this condition. There was a negative correlation between hemoglobin level and HAMD-17 score in all patients. A binary logistic regression analysis revealed that anemia was independently associated with PSD after adjustment for sex, National Institutes of Health Stroke Scale scores, mRS (modified Rankin Scale) scores, BI (Barthel Index) scores, RBC (red blood cell), and hematocrit. In conclusion, anemia at admission is associated with PSD seen in these patients 1 month later. Therefore, anemia is a possible predictor of PSD.

Sodium Butyrate Attenuates Diarrhea in Weaned Piglets and Promotes Tight Junction Protein Expression in Colon in a GPR109A-Dependent Manner.

BACKGROUND/AIMS: Butyric acid plays an important role in maintaining intestinal health. Butyric acid has received special attention as a short-chain fatty acid, but its role in protecting the intestinal barrier is poorly characterized. Butyric acid not only provides energy for epithelial cells but also acts as a histone deacetylase inhibitor; it is also a natural ligand for G protein-coupled receptor 109A (GPR109A). A GPR109A analog was expressed in Sus scrofa and mediated the anti-inflammatory effects of beta-hydroxybutyric acid. This study investigated the effects of butyrate on growth performance, diarrhea symptoms, and tight junction protein levels in 21-day-old weaned piglets. We also studied the mechanism by which butyric acid regulates intestinal permeability. METHODS: Twenty-four piglets that had been weaned at an age of 21 days were divided randomly into 2 equal groups: basal diet group and sodium butyrate + basal diet group. Diarrhea rate, growth performance during 3 weeks of feeding on these diets were observed, the lactulose-mannitol ratio in urine were detected by High Performance Liquid Chromatography, the expression levels of tight junction proteins in the intestinal tract and related signaling molecules, such as GPR109A and Akt, in the colon were examined by quantitative real-time PCR or western blot analyses on day 21. Caco-2 cells were used as a colon cell model and cultured with or without sodium butyrate to assess the expression of tight junction proteins and the activation of related signaling molecules. GPR109A-short hairpin RNA (shRNA) and specific antagonists of Akt and ERK1/2 were used as signaling pathway inhibitors to elucidate the mechanism by which butyric acid regulates the expression of tight junction proteins and the colonic epithelial barrier. RESULTS: The sodium butyrate diet alleviated diarrhea symptoms and decreased intestinal permeability without affecting the growth of early weaned piglets. The expression levels of the tight junction proteins Claudin-3, Occludin, and zonula occludens 1 were up-regulated by sodium butyrate in the colon and Caco-2 cells. GPR109A knockdown using shRNA or blockade of the Akt signaling pathway in Caco-2 cells suppressed sodium butyrate-induced Claudin-3 expression. CONCLUSIONS: Sodium butyrate acts on the Akt signaling pathway to facilitate Claudin-3 expression in the colon in a GPR109A-dependent manner.

High-Density Droplet Microarray of Individually Addressable Electrochemical Cells.

Microarray technology has shown great potential for various types of high-throughput screening applications. The main read-out methods of most microarray platforms, however, are based on optical techniques, limiting the scope of potential applications of such powerful screening technology. Electrochemical methods possess numerous complementary advantages over optical detection methods, including its label-free nature, capability of quantitative monitoring of various reporter molecules, and the ability to not only detect but also address compositions of individual compartments. However, application of electrochemical methods for the purpose of high-throughput screening remains very limited. In this work, we develop a high-density individually addressable electrochemical droplet microarray (eDMA). The eDMA allows for the detection of redox-active reporter molecules irrespective of their electrochemical reversibility in individual nanoliter-sized droplets. Orthogonal band microelectrodes are arranged to form at their intersections an array of three-electrode systems for precise control of the applied potential, which enables direct read-out of the current related to analyte detection. The band microelectrode array is covered with a layer of permeable porous polymethacrylate functionalized with a highly hydrophobic-hydrophilic pattern, forming spatially separated nanoliter-sized droplets on top of each electrochemical cell. Electrochemical characterization of single droplets demonstrates that the underlying electrode system is accessible to redox-active molecules through the hydrophilic polymeric pattern and that the nonwettable hydrophobic boundaries can spatially separate neighboring cells effectively. The eDMA technology opens the possibility to combine the high-throughput biochemical or living cell screenings using the droplet microarray platform with the sequential electrochemical read-out of individual droplets.

AMP010014A09 in Sus Scrofa Encodes an Analog of G Protein-Coupled Receptor 109A, Which Mediates the Anti-Inflammatory Effects of Beta-Hydroxybutyric Acid.

BACKGROUND: Hydroxy-carboxylic acid receptor 2 (HCA2, also called GPR109A) belongs to the G protein-coupled receptor (GPCR) family and is found in humans, rats, mice, hamsters and guinea pigs, but there are almost no reports of this protein in other species. In this investigation, we speculated that AMP010014A09 (AMP+) is a homologue of GPR109A in swine. METHODS: To test this hypothesis, the following experiments were designed: monocytes isolated from the peripheral blood of swine were treated with LPS after pretreating with or without ß-hydroxybutyric acid (BHBA), and the levels of pro-inflammatory cytokines and inflammatory proteins were assessed. cAMP levels induced by Forskolin in swine testicular (ST) and IPEC-J2 cells were detected with or without BHBA treatment and following silencing or stable transfection of the AMP+ gene. RESULTS: AMP+ in swine exhibited a high level of homology with HM74A in humans and PUMA-G in mice. BHBA inhibited the LPS-induced secretion of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß and the inflammatory protein COX-2 in monocytes of swine. BHBA suppressed the Forskolin-induced cAMP level increase in ST cells, but failed to inhibit the accumulation of cAMP after the AMP+ gene was silenced with shRNA by transfecting cells with the pGPU6-GFP-Neo-AMP+-sus-392 plasmid. BHBA had no effect on cAMP levels in IPEC-J2 cells, but significantly inhibited the increase in cAMP induced by Forskolin treatment following transfection of the AMP+ gene into IPEC-J2 cells by a lentivirus vector. CONCLUSION: Our results indicated that AMP+ encodes a G protein-coupled receptor in Sus scrofa that inhibits cAMP levels and mediates anti-inflammatory effects in swine monocytes.

Reactive superhydrophobic surface and its photoinduced disulfide-ene and thiol-ene (bio)functionalization.

Reactive superhydrophobic surfaces are highly promising for biotechnological, analytical, sensor, or diagnostic applications but are difficult to realize due to their chemical inertness. In this communication, we report on a photoactive, inscribable, nonwettable, and transparent surface (PAINTS), prepared by polycondensation of trichlorovinylsilane to form thin transparent reactive porous nanofilament on a solid substrate. The PAINTS shows superhydrophobicity and can be conveniently functionalized with the photoclick thiol-ene reaction. In addition, we show for the first time that the PAINTS bearing vinyl groups can be easily modified with disulfides under UV irradiation. The effect of superhydrophobicity of PAINTS on the formation of high-resolution surface patterns has been investigated. The developed reactive superhydrophobic coating can find applications for surface biofunctionalization using abundant thiol or disulfide bearing biomolecules, such as peptides, proteins, or antibodies.

UV-Induced Disulfide Formation and Reduction for Dynamic Photopatterning.

UV-induced disulfide formation (UV-DF) and disulfide reduction (UV-DR) reactions for surface functionalization and dynamic photopatterning are presented. Both photochemical reactions allow for the spatially and temporally controlled, reversible transition between thiol- and disulfide-functionalized surfaces. The dynamic photopatterning strategy was demonstrated by the UV-induced attachment, exchange, and detachment on thiol-modified substrates.

UV-Induced Tetrazole-Thiol Reaction for Polymer Conjugation and Surface Functionalization.

A UV-induced 1,3-dipolar nucleophilic addition of tetrazoles to thiols is described. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV-induced tetrazole-thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer-polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site-selective surface functionalization. Superhydrophobic-hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole-modified porous polymer surface with hydrophobic and hydrophilic thiols. A biotin-functionalized surface could be fabricated in aqueous solutions under long-wavelength UV irradiation.

Compact Micropatterned Chip Empowers Undisturbed and Programmable Drug Addition in High-Throughput Cell Screening.

Simultaneously adding multiple drugs and other chemical reagents to individual droplets at specific time points presents a significant challenge, particularly when dealing with tiny droplets in high-throughput screening applications. In this study, a micropatterned polymer chip is developed as a miniaturized platform for light-induced programmable drug addition in cell-based screening. This chip incorporates a porous superhydrophobic polymer film with atom transfer radical polymerization reactivity, facilitating the efficient grafting of azobenzene methacrylate, a photoconformationally changeable group, onto the hydrophilic regions of polymer matrix at targeted locations and with precise densities. By employing light irradiation, the cyclodextrin-azobenzene host-guest complexes formed on the polymer chip can switch from an "associated" to a "dissociated" state, granting precise photochemical control over the supramolecular coding system and its surface patterning ability. Significantly, the exceptional spatial and temporal control offered by these chemical transitions empowers to utilize digital light processing systems for simultaneous regulation and release of cyclodextrin-bearing drugs across numerous droplets containing suspended or adhered cells. This approach minimizes mechanical disruption while achieving precise control over the timing of addition, dosage, and integration varieties of released drugs in high-throughput screening, all programmable to meet specific requirements.

Mendelian randomization identifies causal effects of major depressive disorder on accelerated aging.

BACKGROUND: Evidence links major depressive disorder (MDD) with aging, but it's unclear if MDD accelerates aging and what factors mediate this transition. METHODS: Two-sample Mendelian randomization (MR) analyses were applied to estimate the causal association between MDD and frailty index (FI), telomere length (TL), and appendicular lean mass (ALM) from available genome-wide association studies in populations of European ancestry. Furthermore, we conducted mediation MR analyses to assess the mediating effects of 31 lifestyle factors or diseases on the causal relationship between MDD and aging. RESULTS: MDD was significantly causally associated with increased FI (ßIVW = 0.23, 95 % CI = 0.18 to 0.28, p = 1.20 × 10-17), shorter TL (ßIVW = -0.04, 95 % CI = -0.07 to -0.01, p = 0.01), and decreased ALM (ßIVW = -0.07, 95 % CI = -0.11 to -0.03, p = 3.54 × 10-4). The mediation analysis through two-step MR revealed smoking initiation (9.09 %), hypertension (6.67 %) and heart failure (5.36 %) mediated the causal effect of MDD on FI. Additionally, alcohol use disorders and alcohol dependence on the causal relationship between MDD and TL were found to be 17.52 % and 17.13 % respectively. LIMITATIONS: Confounding, statistical power, and Euro-centric focus limit generalization. CONCLUSION: Overall, individuals with MDD may be at a higher risk of experiencing premature aging, and this risk is partially influenced by the pathways involving smoking, alcohol use, and cardiovascular health. It underscores the importance of early intervention and comprehensive health management in individuals with MDD to promote healthy aging and overall well-being.

Liquid-in-liquid printing of 3D and mechanically tunable conductive hydrogels.

Conductive hydrogels require tunable mechanical properties, high conductivity and complicated 3D structures for advanced functionality in (bio)applications. Here, we report a straightforward strategy to construct 3D conductive hydrogels by programable printing of aqueous inks rich in poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) inside of oil. In this liquid-in-liquid printing method, assemblies of PEDOT:PSS colloidal particles originating from the aqueous phase and polydimethylsiloxane surfactants from the other form an elastic film at the liquid-liquid interface, allowing trapping of the hydrogel precursor inks in the designed 3D nonequilibrium shapes for subsequent gelation and/or chemical cross-linking. Conductivities up to 301 S m-1 are achieved for a low PEDOT:PSS content of 9 mg mL-1 in two interpenetrating hydrogel networks. The effortless printability enables us to tune the hydrogels' components and mechanical properties, thus facilitating the use of these conductive hydrogels as electromicrofluidic devices and to customize near-field communication (NFC) implantable biochips in the future.

Patterns of attentional bias in antenatal depression: an eye-tracking study.

Introduction: One of the most common mental disorders in the perinatal period is depression, which is associated with impaired emotional functioning due to alterations in different cognitive aspects including thought and facial emotion recognition. These functional impairment may affect emerging maternal sensitivity and have lasting consequences for the dyadic relationship. The current study aimed to investigate the impact of depressive symptoms on the attention bias of infant stimuli during pregnancy. Methods: Eighty-six pregnant women completed the Edinburgh Postnatal Depression Scale and an eye-tracking task comprising infant-related emotion images. All participants showed biased attention to infant-related images. Results: First, compared to healthy pregnant women, pregnant women with depression symptoms initially directed their attention to infant-related stimuli more quickly (F (1, 84) = 6.175, p = 0.015, η2 = 0.068). Second, the two groups of pregnant women paid attention to the positive infant stimuli faster than the neutral infant stimuli, and the first fixation latency bias score was significantly smaller than that of the infant-related negative stimulus (p = 0.007). Third, compared with the neutral stimulus, the non-depression group showed a longer first gaze duration to the negative stimulus of infants (p = 0.019), while the depressive symptoms group did not show this difference. Conclusion: We speculate that structural and functional changes in affective motivation and cognitive-attention brain areas may induce these attentional bias patterns. These results provide suggestions for the implementation of clinical intervention programs to correct the attention bias of antenatal depressed women.

Quadruple-responsive nanocomposite based on dextran-PMAA-PNIPAM, iron oxide nanoparticles, and gold nanorods.

A quadruple-responsive nanocomposite that responds to temperature, pH, magnetic field, and NIR is obtained by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and gold nanorods (AuNRs) into a dextran-based smart copolymer network. The dual-sensitive copolymer is prepared by sequential RAFT polymerization of methacrylic acid and N-isopropylacrylamide from trithiocarbonate groups linked to dextran in one pot. These functionalized nanocomposites with superior stability can respond to the four stimuli mentioned above well. As evidenced by UV-vis and TEM measurements, the temperature-induced unusual blue-shift in the longitudinal plasmon band is possibly due to the side-to-side assembly of AuNRs.

A Reactive Superhydrophobic Platform for Living Photolithography.

Superhydrophobic surfaces with regional functions have widespread applications in biotechnology, diagnostic applications, and micro-chemical synthesis and analysis. However, owing to their chemical inertness, superhydrophobic surfaces with chemical reactivity are difficult to achieve. Superhydrophobic surfaces that can be further modified with varied densities and expanded species of the functional moieties are not readily available. In this study, a single-step approach to achieve a reactive superhydrophobic surface is reported, on which chemical grafting of a library of molecules can be carried out through surface-initiated atom-transfer radical addition or surface-initiated atom-transfer radical polymerization. The excellent spatial and temporal controllability of these chemical processes under visible light enables us to take advantage of programmed liquid-crystal-display (LCD) or Digital Light Processing (DLP) photolithography systems to effortlessly regulate the location, density, and species of the functional molecules on the reactive superhydrophobic surface. The distinctive properties of this surface will provide new insight into intelligent superhydrophobic material development and practical applications, such as aqueous/oil microdroplets array, multi-anti-counterfeiting labels and integrated microfluidic reactors with enzymes for chemical logic learning.

1D micro-nanopatterned integrin ligand surfaces for directed cell movement.

Cell-extracellular matrix (ECM) adhesion mediated by integrins is a highly regulated process involved in many vital cellular functions such as motility, proliferation and survival. However, the influence of lateral integrin clustering in the coordination of cell front and rear dynamics during cell migration remains unresolved. For this purpose, we describe a novel protocol to fabricate 1D micro-nanopatterned stripes by integrating the block copolymer micelle nanolithography (BCMNL) technique and maskless near UV lithography-based photopatterning. The photopatterned 10 µm-wide stripes consist of a quasi-perfect hexagonal arrangement of gold nanoparticles, decorated with the RGD (arginine-glycine-aspartate) motif for single integrin heterodimer binding, and placed at a distance of 50, 80, and 100 nm to regulate integrin clustering and focal adhesion dynamics. By employing time-lapse microscopy and immunostaining, we show that the displacement and speed of fibroblasts changes according to the nanoscale spacing of adhesion sites. We found that as the lateral spacing of adhesive peptides increased, fibroblast morphology was more elongated. This was accompanied by a decreased formation of mature focal adhesions and stress fibers, which increased cell displacement and speed. These results provide new insights into the migratory behavior of fibroblasts in 1D environments and our protocol offers a new platform to design and manufacture confined environments in 1D for integrin-mediated cell adhesion.

Temperature- and redox-directed multiple self assembly of poly(N-isopropylacrylamide) grafted dextran nanogels.

Poly(N-isopropylacrylamide) (PNIPAAm) grafted dextran nanogels with dodecyl and thiol end groups have been synthesized by RAFT process. Dodecyl-terminated polymers (DexPNI) can be readily dissolved in water and further self assemble into ordered stable nanostructures through direct noncovalent interactions at room temperature. SEM, AFM and DLS measurements confirm the formation of spherical nanogels at hundred-nanometer scales. The elevation of environment temperature will indirectly result in the formation of collapsed nanostructures due to the LCST phase transition of PNIPAAm side chains. Turbidimetry results show that the phase transition behaviors of DexPNI are greatly dependent on PNIPAAm chain length and polymer concentration: increasing PNIPAAm chain length and polymer concentration both lead to lower LCSTs and sharper phase transitions. Moreover, the dodecyl-terminated polymers can transform into thiol-terminated versions by aminolysis of trithiocarbonate groups, and further into chemical (disulfide) cross-linked versions (SS-DexPNI) by oxidation. SS-DexPNI nanogels have "doubled" chain length of PNIPAAm, and hence sharper phase transitions. In situ DLS measurements of the evolution of hydrodynamic radius attest that the self assembly of SS-DexPNI nanogels can be selectively directed by the change in either external temperature or redox potential. These nanogels thus are promising candidates for triggered intracellular delivery of encapsulated cargo. We can also expect that the polymer can be noncovalently (by dodecyl end groups) or covalently (by thiol end groups) coated on a series of nanomaterials (e.g., carbon nanotubes, graphene, gold nanomaterials) to build a variety of novel smart, and robust nanomaterials.

Risk factors for postpartum depression in Chinese women: A cross-sectional study at 6 weeks postpartum.

OBJECTIVE: Postpartum depression (PPD) has received increasing attention due to its harmful impacts and high incidence. PPD is affected by physiological and psychological factors, but the conclusions are not uniform at present, so this study explored the risk factors of postpartum depressive symptoms (PPDS) in Chinese population. METHODS: A total of 397 women attending the obstetric department of the First Affiliated Hospital of Wenzhou Medical University participated in the questionnaire survey, mainly through a cross sectional study. At 6 weeks postpartum, the Edinburgh Postpartum Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess PPDS and sleep quality, respectively. RESULTS: The incidence of probable PPDS in our study population was 14.6% at 6 weeks postpartum. Women with blood group A had an almost 3-fold greater risk of PPDS than those with blood group B (OR [95% CI], 2.99 [1.43-6.28], p = 0.004). After adjusting for potential confounding variables, the blood group A phenotype was significantly more prevalent in women with PPDS compared to blood group B (OR [95% CI], 2.65 [1.23-5.70], p = 0.01). CONCLUSIONS: Compared to women with blood groups B, AB or O, women with blood group A had high odds of PPDS. If this result can be demonstrated and replicated in other populations, blood group A may be a useful predictor of risk for PPDS in Chinese postpartum women.

Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma.

The prognosis of most patients with papillary thyroid carcinoma (PTC) is excellent despite some cases of tumor progression or relapse. The present study was designed to reveal possible prognostic risk indicators for PTC. Differentially expressed genes (DEGs) extracted from 4 Gene Expression Omnibus (GEO) cohorts were subjected to functional enrichment analyses by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. A dataset from The Cancer Genome Atlas (TCGA) was obtained to filter and validate significant genes using cytoHubba, followed by analysis of their association with clinicopathological characteristics and prognosis. In total, 240 DEGs were identified after data preprocessing. These DEGs were enriched in 'intracellular redox equilibrium', 'release of exosome', 'cell adhesion', 'regulation of extracellular matrix', 'collagen binding' and 'energy metabolism' based on GO analysis which including cellular component, molecular function and biological process. KEGG pathway analysis revealed that the DEGs were enriched in thyroid hormone synthesis, pathways in cancer, focal adhesion, metabolic pathways, apoptosis, PPAR signaling pathway and PI3K/AKT signaling pathway. Using cytoHubba, the following hub genes were identified: Apolipoprotein E (APOE); hemoglobin subunit α1 (HBA1); angiotensin II receptor 1 (AGTR1); collagen I α1 (COL1A1); galectin 3 (LGALS3) and TIMP metallopeptidase inhibitor 1 (TIMP1). The expression of these genes was found to be consistent in TCGA datasets. Kaplan-Meier analysis revealed that APOE was significantly associated with overall survival (P=0.00067) and disease free survival (P=0.00220). Additionally, low expression of APOE was significantly associated with older age (P<0.001) and higher TNM stage (P<0.001) compared with the high expression group. Therefore, APOE may function as a predictive risk indicator for progression as well as prognosis of PTC.

A Unique B-Family DNA Polymerase Facilitating Error-Prone DNA Damage Tolerance in Crenarchaeota.

Sulfolobus islandicus codes for four DNA polymerases: three are of the B-family (Dpo1, Dpo2, and Dpo3), and one is of the Y-family (Dpo4). Western analysis revealed that among the four polymerases, only Dpo2 exhibited DNA damage-inducible expression. To investigate how these DNA polymerases could contribute to DNA damage tolerance in S. islandicus, we conducted genetic analysis of their encoding genes in this archaeon. Plasmid-borne gene expression revealed that Dpo2 increases cell survival upon DNA damage at the expense of mutagenesis. Gene deletion studies showed although dpo1 is essential, the remaining three genes are dispensable. Furthermore, although Dpo4 functions in housekeeping translesion DNA synthesis (TLS), Dpo2, a B-family DNA polymerase once predicted to be inactive, functions as a damage-inducible TLS enzyme solely responsible for targeted mutagenesis, facilitating GC to AT/TA conversions in the process. Together, our data indicate that Dpo2 is the main DNA polymerase responsible for DNA damage tolerance and is the primary source of targeted mutagenesis. Given that crenarchaea encoding a Dpo2 also have a low-GC composition genome, the Dpo2-dependent DNA repair pathway may be conserved in this archaeal lineage.