Bibliometric analysis of kinship analysis from 1960 to 2023: global trends and development.

Kinship analysis is a crucial aspect of forensic genetics. This study analyzed 1,222 publications on kinship analysis from 1960 to 2023 using bibliometric analysis techniques, investigating the annual publication and citation patterns, most productive countries, organizations, authors and journals, most cited documents and co-occurrence of keywords. The initial publication in this field occurred in 1960. Since 2007, there has been a significant increase in publications, with over 30 published annually except for 2010. China had the most publications (n = 213, 17.43%), followed by the United States (n = 175, 14.32%) and Germany (n = 89, 7.28%). The United States also had the highest citation count. Sichuan University in China has the largest number of published articles. The University of Leipzig and the University of Cologne in Germany exhibit the highest total citation count and average citation, respectively. Budowle B was the most prolific author and Kayser M was the most cited author. In terms of publications, Forensic Science International- Genetics, Forensic Science International, and International Journal of Legal Medicine were the most prolific journals. Among them, Forensic Science International-Genetics boasted the highest h-index, citation count, and average citation rate. The most frequently cited publication was "Van Oven M, 2009, Hum Mutat", with a total of 1,361 citations. The most frequent co-occurrence keyword included "DNA", "Loci", "Paternity testing", "Population", "Markers", and "Identification", with recent interest focusing on "Kinship analysis", "SNP" and "Inference". The current research is centered around microhaplotypes, forensic genetic genealogy, and massively parallel sequencing. The field advanced with new DNA analysis methods, tools, and genetic markers. Collaborative research among nations, organizations, and authors benefits idea exchange, problem-solving efficiency, and high-quality results.

Mutant huntingtin protein induces MLH1 degradation, DNA hyperexcision, and cGAS-STING-dependent apoptosis.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The repeat-expanded HTT encodes a mutated HTT (mHTT), which is known to induce DNA double-strand breaks (DSBs), activation of the cGAS-STING pathway, and apoptosis in HD. However, the mechanism by which mHTT triggers these events is unknown. Here, we show that HTT interacts with both exonuclease 1 (Exo1) and MutLα (MLH1-PMS2), a negative regulator of Exo1. While the HTT-Exo1 interaction suppresses the Exo1-catalyzed DNA end resection during DSB repair, the HTT-MutLα interaction functions to stabilize MLH1. However, mHTT displays a significantly reduced interaction with Exo1 or MutLα, thereby losing the ability to regulate Exo1. Thus, cells expressing mHTT exhibit rapid MLH1 degradation and hyperactive DNA excision, which causes severe DNA damage and cytosolic DNA accumulation. This activates the cGAS-STING pathway to mediate apoptosis. Therefore, we have identified unique functions for both HTT and mHTT in modulating DNA repair and the cGAS-STING pathway-mediated apoptosis by interacting with MLH1. Our work elucidates the mechanism by which mHTT causes HD.

A preliminary report on the exploration of salivary bacterial diversity by the multiplex SNaPshot assay.

Salivary bacterial community composition is associated with the host's internal and environmental factors, which have potential applications in forensic practice. The 16S rRNA gene sequencing is the most commonly used strategy for detecting salivary bacterial diversity; however, its platforms are not compatible with capillary electrophoresis (CE) platforms commonly used for forensic applications. Therefore, we attempted to detect the salivary bacterial diversity using a single nucleotide polymorphism (SNP) assay. Salivary bacterial diversity varies among diverse geographic locations, making it a potential supplementary biomarker for forensic geographic sourcing. To evaluate the performance of the multiplex SNaPshot assay, saliva samples from three geographic locations in China were analyzed using the multiplex SNaPshot assay and 16S rRNA gene sequencing. We screened SNPs from two high-relative-abundance salivary genera (Streptococcus and Veillonella) to construct a multiplex SNaPshot system that can be used on the CE platform. The stability and sensitivity of the multiplex SNaPshot system were also tested. A random forest classification model was used to classify samples from different regions to explore the ability of salivary bacteria to discriminate between geographic sources. Six bacterial SNPs were screened and a multiplex SNaPshot system was constructed. The stability results showed that the typing of salivary stains that were placed indoors for different days was not affected in this study. Two-thirds of mocked salivary stain samples showed more than 90% of typing results obtained for salivary stain samples with an input of 0.1 µl saliva. The results of principal coordinate analysis based on salivary bacterial diversity showed significant differences between samples from the three different geographic locations. The accuracy of the random forest classification was 66.67% based on the multiplex SNaPshot assay and 83.33% based on the 16S rRNA gene sequencing. In conclusion, this is the first attempt to detect salivary bacterial diversity using a multiplex SNaPshot bacterial SNP assay. The geographic difference in human salivary bacterial community composition was significant, as revealed by the multiplex SNaPshot assay; however, its performance in discriminating geographic sources was lower than that of 16S rRNA gene sequencing. This strategy based on bacterial SNP loci may favor the detection of human bacterial diversity in common forensic laboratories but requires further exploration in larger sample sizes and more bacterial SNP loci.

Heat shock protein DNAJA2 regulates transcription-coupled repair by triggering CSB degradation via chaperone-mediated autophagy.

Transcription-coupled nucleotide excision repair (TC-NER) is an important genome maintenance system that preferentially removes DNA lesions on the transcribed strand of actively transcribed genes, including non-coding genes. TC-NER involves lesion recognition by the initiation complex consisting of RNA polymerase II (Pol II) and Cockayne syndrome group B (CSB), followed by NER-catalyzed lesion removal. However, the efficient lesion removal requires the initiation complex to yield the right of way to the excision machinery, and how this occurs in a timely manner is unknown. Here we show that heat shock protein DNAJA2 facilitates the HSC70 chaperone-mediated autophagy (CMA) to degrade CSB during TC-NER. DNAJA2 interacts with and enables HSC70 to recognize sumoylated CSB. This triggers the removal of both CSB and Pol II from the lesion site in a manner dependent on lysosome receptor LAMP2A. Defects in DNAJA2, HSC70 or LAMP2A abolish CSB degradation and block TC-NER. Our findings discover DNAJA2-mediated CMA as a critical regulator of TC-NER, implicating the DNAJA2-HSC70-CMA axis factors in genome maintenance.

DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability.

Molecular chaperone HSP70s are attractive targets for cancer therapy, but their substrate broadness and functional non-specificity have limited their role in therapeutical success. Functioning as HSP70's cochaperones, HSP40s determine the client specificity of HSP70s, and could be better targets for cancer therapy. Here we show that tumors defective in HSP40 member DNAJA2 are benefitted from immune-checkpoint blockade (ICB) therapy. Mechanistically, DNAJA2 maintains centrosome homeostasis by timely degrading key centriolar satellite proteins PCM1 and CEP290 via HSC70 chaperone-mediated autophagy (CMA). Tumor cells depleted of DNAJA2 or CMA factor LAMP2A exhibit elevated levels of centriolar satellite proteins, which causes aberrant mitosis characterized by abnormal spindles, chromosome missegregation and micronuclei formation. This activates the cGAS-STING pathway to enhance ICB therapy response in tumors derived from DNAJA2-deficient cells. Our study reveals a role for DNAJA2 to regulate mitotic division and chromosome stability and suggests DNAJA2 as a potential target to enhance cancer immunotherapy, thereby providing strategies to advance HSPs-based cancer therapy.

A bibliometric analysis of microbial forensics from 1984 to 2022: progress and research trends.

Microbial forensics is a rapidly evolving discipline that has gained significant momentum in recent years. The study evaluated relevant results over the last four decades from 1984 to 2022 all over the world, aiming to analyze the growing trends and research orientations of microbial forensics. Using "microbial forensics" as the search topic in the Web of Science Core Collection, the systematic retrieval identified 579 documents relevant to the field and draw many statistical tables and maps to make the retrieval results visible. According to further bibliometric analysis, there are an increasing number of publications related to microbial forensics from the overall trend, with the highest number of publications recorded in 2021. In terms of the total number of articles, the USA and China were both the leading contributors to the field among 40 countries. The field has developed rapidly in recent years based on the development of next-generation sequencing. Over the course of its development, there are rich keywords in the research of scholars, which focus on diversity and identification. Moreover, despite the early hot topic being PCR (the use of PCR to probe microorganisms), in recent years, the topics, markers, and the potential application of microorganisms in forensic practice have become hot, which also indicates the future research directions of microbial forensic.

Fermented dairy foods consumption and depressive symptoms: A meta-analysis of cohort studies.

BACKGROUND: The gut-brain axis has been potentially proposed as a link between the intake of fermented dairy foods and depression. We carried out this meta-analysis on published cohort studies to estimate the overall depression risk of fermented dairy foods intake. METHODS: We searched the CNKI (China National Knowledge Infrastructure) and PubMed databases for all articles within a range of published years from 2010 to 2022 on the association between fermented dairy foods intake and depression. RESULTS: Finally, 8 studies met the inclusion criteria for this study, with 83,533 participants. Overall, there was statistical evidence of significantly decreased depression risk was found to be associated with fermented dairy foods intake (OR = 0.89, 95% CI = 0.81-0.98). In subgroup analysis, cheese and yogurt consumptions were significantly associated with decreased depression risk (OR = 0.91, 95% CI = 0.84-0.98 for cheese and OR = 0. 84, 95% CI = 0.72-0.99 for yogurt). However, we failed to find superabundant intake of fermented dairy foods intake decreased the risk of depression. CONCLUSION: Our meta-analysis indicated that fermented dairy foods intake may have potential beneficial effect on depression via the gut-brain axis.

Preparation of shell-core fiber-encapsulated Lactobacillus rhamnosus 1.0320 using coaxial electrospinning.

In this study, shell-core fibers were successfully prepared by using Eudragit S100 (ES100) and poly(vinyl alcohol) (PVA)/pectin (PEC) through coaxial electrospinning technology. The electrospun fiber was characterized by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Thermo-gravimetric analysis (TGA) showed that the coaxial electrospun fiber encapsulated with Lactobacillus rhamnosus 1.0320 (L. rhamnosus) had higher thermal stability than the electrospun fiber prepared by uniaxial electrospinning. L. rhamnosus encapsulated by coaxial electrospun fiber maintained 90.07% and 91.96% survivability in simulated gastric and intestinal fluids. After continuous simulated gastrointestinal fluid treatment, the survival rate of L. rhamnosus encapsulated by coaxial electrospun fiber was 81.40%. The results indicate that shell-core fiber-encapsulated probiotics can improve the tolerance of probiotics to the harsh environment of gastrointestinal tract. The fiber prepared in this study can be applied to the preparation of functional fermented food such as probiotic yogurt fermentation in the future.

Reproducibility and Validity of a Semi-Quantitative Food Frequency Questionnaire for Assessing Dietary Intake of Vegetarians and Omnivores in Harbin, China.

This study aims to evaluate the reproducibility and validity of a semi-quantitative food frequency questionnaire (SQFFQ) developed for vegetarians and omnivores in Harbin, China. Participants (36 vegetarians and 64 omnivores) administered SQFFQ at baseline (SQFFQ1) and six months later (SQFFQ2) to assess the reproducibility. The 24 h recalls (24 HRs) for three consecutive days were completed between the administrations of two SQFFQs to determine the validity. For reproducibility, Pearson correlation coefficients between SQFFQ1 and SQFFQ2 for vegetarians and omnivores were 0.45~0.88 and 0.44~0.84, respectively. For validity, unadjusted Pearson correlation coefficients were 0.46~0.83 with an average of 0.63 and 0.43~0.86 with an average of 0.61, respectively; energy-adjusted Pearson correlation coefficients were 0.43~0.82 with an average of 0.61 and 0.40~0.85 with an average of 0.59, respectively. Majority of the correlation coefficients for food groups and macronutrients decreased or remained unchanged after energy adjustment. Furthermore, all correlations were statistically significant (p < 0.05). Bland−Altman plots also showed reasonably acceptable agreement between the two methods. In conclusion, the SQFFQ developed in this study has reasonably acceptable reproducibility and validity.

Soybean-Oil-Body-Substituted Low-Fat Ice Cream with Different Homogenization Pressure, Pasteurization Condition, and Process Sequence: Physicochemical Properties, Texture, and Storage Stability.

The purpose of this research was to explore the impacts of different homogenization pressures, pasteurization conditions, and process sequence on the physical and chemical properties of soybean oil body (SOB)-substituted low-fat ice cream as well as the storage stability of SOB-substituted ice cream under these process parameters. With the increase of homogenization pressure (10-30 MPa), the increase of pasteurization temperature (65 °C for 30 min-85 °C for 15 min), and the addition of SOB before homogenization, the overrun and apparent viscosity of ice cream increased significantly, and the particle size, hardness, and melting rate decreased significantly. Thus, frozen dairy products of desired quality and condition could be obtained by optimizing process parameters. In addition, the SOB ice cream showed better storage stability, which was reflected in lower melting rate and hardness and more stable microstructure compared with the full-milk-fat ice cream. This study opened up new ideas for the application of SOB and the development of nutritious and healthy ice cream. Meanwhile, this research supplied a conceptual basis for the processing and quality optimization of SOB ice cream.

The mismatch recognition protein MutSα promotes nascent strand degradation at stalled replication forks.

Mismatch repair (MMR) is a replication-coupled DNA repair mechanism and plays multiple roles at the replication fork. The well-established MMR functions include correcting misincorporated nucleotides that have escaped the proofreading activity of DNA polymerases, recognizing nonmismatched DNA adducts, and triggering a DNA damage response. In an attempt to determine whether MMR regulates replication progression in cells expressing an ultramutable DNA polymerase ɛ (Polɛ), carrying a proline-to-arginine substitution at amino acid 286 (Polɛ-P286R), we identified an unusual MMR function in response to hydroxyurea (HU)-induced replication stress. Polɛ-P286R cells treated with hydroxyurea exhibit increased MRE11-catalyzed nascent strand degradation. This degradation by MRE11 depends on the mismatch recognition protein MutSα and its binding to stalled replication forks. Increased MutSα binding at replication forks is also associated with decreased loading of replication fork protection factors FANCD2 and BRCA1, suggesting blockage of these fork protection factors from loading to replication forks by MutSα. We find that the MutSα-dependent MRE11-catalyzed fork degradation induces DNA breaks and various chromosome abnormalities. Therefore, unlike the well-known MMR functions of ensuring replication fidelity, the newly identified MMR activity of promoting genome instability may also play a role in cancer avoidance by eliminating rogue cells.

Physicochemical properties and bioactivity of polysaccharides from Isaria cicadae Miquel with different extraction processes: effects on gut microbiota and immune response in mice.

The effect of different extraction processes on the physicochemical characterization, digestibility, antioxidant activity and prebiotic activity of Isaria cicadae Miquel (ICM) fruiting body polysaccharides was studied. Furthermore, the effect of ultrasound-assisted extraction of ICM (U-ICM) on gut microbiota, the intestinal barrier and immune response was deeply explored. This study found that ICMs showed high indigestibility in both α-amylase and artificial gastric juice, indicating that ICMs have the potential as dietary fiber. In contrast, U-ICM had the best antioxidant activity and prebiotic potential. Meanwhile, there was a structure-activity relationship between the antioxidant activity of ICMs and the content of uronic acid, arabinose and galactose. When healthy mice were fed U-ICM for 42 days, the relative abundances of Lactobacillus, Akkermansia, and Bacteroides were found to increase significantly, while that of Clostridium decreased significantly. Meanwhile, U-ICM significantly promotes the expression of tight junction protein and the production of cytokines, indicating that U-ICM had the function of enhancing the intestinal barrier and regulating the host immune response. In conclusion, U-ICM as dietary fiber has the potential to be developed as a gut health-promoting prebiotic component or functional food. This research provided a valuable resource for further exploring the structure-activity relationship and prebiotic activity of ICMs.

Lactobacillus plantarum Combined with Galactooligosaccharides Supplement: A Neuroprotective Regimen Against Neurodegeneration and Memory Impairment by Regulating Short-Chain Fatty Acids and the c-Jun N-Terminal Kinase Signaling Pathway in Mice.

Probiotics and prebiotics have received attention in alleviating neurodegenerative diseases. Lactobacillus plantarum (L. plantarum) 69-2 was combined with galactooligosaccharides (GOS) and supplemented in a d-galactose (d-gal)-induced neurodegeneration and memory impairment mice model to explore its effects on the brain and the regulation of short-chain fatty acids. The results showed that the L. plantarum-GOS supplementation inhibited d-gal-induced oxidative stress and increased the brain's nuclear factor erythroid 2-related factor 2 (Nrf2) levels. Butyrate, a metabolite of the gut microbiota regulated by L. plantarum combined with GOS, inhibits p-JNK expression, downregulates pro-apoptotic proteins expression and the activation of inflammatory mediators, and upregulates synaptic protein expression. This might be a potential mechanism for L. plantarum 69-2 combined with GOS supplementation to alleviate d-gal-induced neurodegeneration and memory impairment. This study sheds new light on the development of aging-related neuroprotective dietary supplements based on the gut-brain axis.

Interplay between H3K36me3, methyltransferase SETD2, and mismatch recognition protein MutSα facilitates processing of oxidative DNA damage in human cells.

Oxidative DNA damage contributes to aging and the pathogenesis of numerous human diseases including cancer. 8-hydroxyguanine (8-oxoG) is the major product of oxidative DNA lesions. Although OGG1-mediated base excision repair is the primary mechanism for 8-oxoG removal, DNA mismatch repair has also been implicated in processing oxidative DNA damage. However, the mechanism of the latter is not fully understood. Here, we treated human cells defective in various 8-oxoG repair factors with H2O2 and performed biochemical, live cell imaging, and chromatin immunoprecipitation sequencing analyses to determine their response to the treatment. We show that the mismatch repair processing of oxidative DNA damage involves cohesive interactions between mismatch recognition protein MutSα, histone mark H3K36me3, and H3K36 trimethyltransferase SETD2, which activates the ATM DNA damage signaling pathway. We found that cells depleted of MutSα or SETD2 accumulate 8-oxoG adducts and fail to trigger H2O2-induced ATM activation. Furthermore, we show that SETD2 physically interacts with both MutSα and ATM, which suggests a role for SETD2 in transducing DNA damage signals from lesion-bound MutSα to ATM. Consistently, MutSα and SETD2 are highly coenriched at oxidative damage sites. The data presented here support a model wherein MutSα, SETD2, ATM, and H3K36me3 constitute a positive feedback loop to help cells cope with oxidative DNA damage.

Effects of Soybean Oil Body as a Milk Fat Substitute on Ice Cream: Physicochemical, Sensory and Digestive Properties.

Soybean oil body (SOB) has potential as a milk fat substitute due to its ideal emulsification, stability and potential biological activity. In this study, SOB was used as a milk fat substitute to prepare ice cream, expecting to reduce the content of saturated fatty acid and improve the quality defects of ice cream products caused by the poor stability of milk fat at low temperatures. This study investigated the effect of SOB as a milk fat substitute (the substitution amount was 10-50%) on ice cream through apparent viscosity, particle size, overrun, melting, texture, sensory and digestive properties. The results show SOB substitution for milk fat significantly increased the apparent viscosity and droplet uniformity and decreased the particle size of the ice cream mixes, indicating that there were lots of intermolecular interactions to improve ice cream stability. In addition, ice cream with 30% to 50% SOB substitution had better melting properties and texture characteristics. The ice cream with 40% SOB substitution had the highest overall acceptability. Furthermore, SOB substitution for milk fat increased unsaturated fatty acid content in ice cream and fatty acid release during digestion, which had potential health benefits for consumers. Therefore, SOB as a milk fat substitute may be an effective way to improve the nutritional value and quality characteristics of dairy products.

Lactobacillus paracasei 24 Attenuates Lipid Accumulation in High-Fat Diet-Induced Obese Mice by Regulating the Gut Microbiota.

Obesity has become a worldwide public health problem. Lactic acid bacteria have attracted extensive attention for alleviating obesity and fat accumulation. This study aimed to evaluate the alleviating effects of Lactobacillus paracasei 24 (LP24) on lipid accumulation in an obese mouse model induced by a high-fat diet (HFD). The results showed that LP24 treatment significantly reduced body weight and fat deposition in HFD mice, improved blood lipid levels and liver steatosis, reduced liver oxidative stress injury and the inflammatory response, and regulated fat metabolism-related factors. Moreover, LP24 regulated the abundance and diversity of the gut microbiota, reduced the abundance of Firmicutes and the ratio of Firmicutes/Bacteroidetes (F/B), and increased the abundance of Akkermansia. In summary, LP24 regulates lipid metabolism by activating the expression level of related genes and regulating the gut microbiota through the gut-liver axis to attenuate the development of obesity. This study provides a theoretical basis for probiotics to regulate gut microbiota to reduce lipid accumulation.

NaCl induces flocculation and lipid oxidation of soybean oil body emulsions recovered by neutral aqueous extraction.

BACKGROUND: Soybean oil bodies (SOB) are naturally pre-emulsified lipid droplets recovered directly from soybean seeds. Almost all food emulsions contain salts. However, it was not clear how the incorporation of salts affected the physicochemical stability of SOB. RESULTS: This study investigated the effect of NaCl (0-1.2%) on the physical and oxidative stability of SOB emulsions under neutral (pH 7) and acidic (pH 3) conditions. In the presence of NaCl, the SOB emulsion (pH 7) showed strong flocculation during storage due to electrostatic screening. The NaCl-induced flocculation of SOB was attenuated at pH 3, which may be due to the difference in conformation or interaction of the protein interfaces covering SOB at different pH values. The increase in ionic strength or acid conditioning treatment resulted in a remarkable increase in the stability of SOB emulsions against coalescence. The confocal laser scanning microscopy images also confirmed the NaCl-induced changes in the flocculation/coalescence properties of SOB. The oxidative behavior tests indicated that SOB emulsions containing NaCl were more susceptible to lipid oxidation but protein oxidation was inhibited due to electrostatic screening, which reduced pro-oxidant accessibility of unadsorbed proteins in the emulsion. This oxidative behavior was attenuated at pH 3. CONCLUSION: The incorporation of NaCl significantly reduced the physical and oxidative stability of the SOB emulsion, and acidic pH mitigated NaCl-induced flocculation and lipid oxidation of SOB. © 2021 Society of Chemical Industry.

Detection of 3D Arterial Centerline Extraction in Spiral CT Coronary Angiography.

This paper presents an in-depth study and analysis of the 3D arterial centerline in spiral CT coronary angiography, and constructs its detection and extraction technique. The first time, the distance transform is used to complete the boundary search of the original figure; the second time, the distance transform is used to calculate the value of the distance transform of all voxels, and according to the value of the distance transform, unnecessary voxels are deleted, to complete the initial contraction of the vascular region and reduce the computational consumption in the next process; then, the nonwitnessed voxels are used to construct the maximum inner joint sphere model and find the skeletal voxels that can reflect the shape of the original figure. Finally, the skeletal lines were optimized on these initially extracted skeletal voxels using a dichotomous-like principle to obtain the final coronary artery centerline. Through the evaluation of the experimental results, the algorithm can extract the coronary centerline more accurately. In this paper, the segmentation method is evaluated on the test set data by two kinds of indexes: one is the index of segmentation result evaluation, including dice coefficient, accuracy, specificity, and sensitivity; the other is the index of clinical diagnosis result evaluation, which is to refine the segmentation result for vessel diameter detection. The results obtained in this paper were compared with the physicians' labeling results. In terms of network performance, the Dice coefficient obtained in this paper was 0.89, the accuracy was 98.36%, the sensitivity was 93.36%, and the specificity was 98.76%, which reflected certain advantages in comparison with the advanced methods proposed by previous authors. In terms of clinical evaluation indexes, by performing skeleton line extraction and diameter calculation on the results obtained by the segmentation method proposed in this paper, the absolute error obtained after comparing with the diameter of the labeled image was 0.382 and the relative error was 0.112, which indicates that the segmentation method in this paper can recover the vessel contour more accurately. Then, the results of coronary artery centerline extraction with and without fine branch elimination were evaluated, which proved that the coronary artery centerline has higher accuracy after fine branch elimination. The algorithm is also used to extract the centerline of the complete coronary artery tree, and the results prove that the algorithm has better results for the centerline extraction of the complete coronary vascular tree.

DNA polymerase θ promotes CAG•CTG repeat expansions in Huntington's disease via insertion sequences of its catalytic domain.

Huntington's disease (HD), a neurodegenerative disease characterized by progressive dementia, psychiatric problems, and chorea, is known to be caused by CAG repeat expansions in the HD gene HTT. However, the mechanism of this pathology is not fully understood. The translesion DNA polymerase θ (Polθ) carries a large insertion sequence in its catalytic domain, which has been shown to allow DNA loop-outs in the primer strand. As a result of high levels of oxidative DNA damage in neural cells and Polθ's subsequent involvement in base excision repair of oxidative DNA damage, we hypothesized that Polθ contributes to CAG repeat expansion while repairing oxidative damage within HTT. Here, we performed Polθ-catalyzed in vitro DNA synthesis using various CAG•CTG repeat DNA substrates that are similar to base excision repair intermediates. We show that Polθ efficiently extends (CAG)n•(CTG)n hairpin primers, resulting in hairpin retention and repeat expansion. Polθ also triggers repeat expansions to pass the threshold for HD when the DNA template contains 35 repeats upward. Strikingly, Polθ depleted of the catalytic insertion fails to induce repeat expansions regardless of primers and templates used, indicating that the insertion sequence is responsible for Polθ's error-causing activity. In addition, the level of chromatin-bound Polθ in HD cells is significantly higher than in non-HD cells and exactly correlates with the degree of CAG repeat expansion, implying Polθ's involvement in triplet repeat instability. Therefore, we have identified Polθ as a potent factor that promotes CAG•CTG repeat expansions in HD and other neurodegenerative disorders.

Screening beneficial bacteriostatic lactic acid bacteria in the intestine and studies of bacteriostatic substances.

Lactic acid bacteria (LAB) are a representative probiotic. As the dominant flora in the human intestinal tract, LAB can regulate the balance of human intestinal flora and improve host health. The purpose of this study was to isolate and screen LAB that are well suited to the intestinal characteristics of the Chinese population, with excellent probiotics and high antibacterial activity. After 16S ribosomal RNA (rRNA) homology and phylogenetic tree analysis, potential probiotics were tested for their antibacterial activity, resistance to artificial gastrointestinal fluid and drugs, surface hydrophobicity, and safety. Three strains of LAB with acid resistance, bile salt resistance, epithelial cell adhesion, and no multidrug resistance were selected: Lactobacillus salivarius, Leuconostoc lactis, and Lactobacillus paracasei. Analysis of the antibacterial active substances in the three strains and their fermentation broths revealed that the main antibacterial substances of L. lactis were organic acids, whereas those of L. salivarius and L. paracasei were organic acids and bacteriocins with broad-spectrum antibacterial activity. These three strains of probiotic LAB with high antibacterial activity were identified as bacterial resources that could potentially be used to develop probiotic preparations for the prevention and treatment of intestinal diseases caused by intestinal pathogens.