Tumour-associated and non-tumour-associated bacteria co-abundance groups in colorectal cancer.

BACKGROUND & AIMS: Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified. METHODS: Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs. RESULTS: Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009). CONCLUSIONS: Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.

From Traditional to Intelligent, A Review of Application and Progress of Sensory Analysis in Alcoholic Beverage Industry.

Sensory analysis is an interdisciplinary field that combines multiple disciplines to analyze food qualitatively and quantitatively. At present, this analysis method has been widely used in product development, quality control, marketing, flavor analysis, safety supervision and inspection of alcoholic beverages. Due to the changing needs of analysis, new and more optimized methods are still emerging. Thereinto, intelligent and biometric technologies with growing attention have also been applied to sensory analysis. This work summarized the sensory analysis methods from three aspects, including traditional artificial sensory analysis, intelligent sensory technology, and innovative technologies. Meanwhile, the application sensory analysis in alcoholic beverages and its industrial production was scientifically emphasized. Moreover, the future tendency of sensory analysis in the alcoholic beverage industry is also highlights.

Genome editing in plants using the TnpB transposase system.

The widely used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is thought to have evolved from IS200/IS605 transposons. TnpB proteins, encoded by one type of IS200/IS605 transposon, are considered to be the evolutionary ancestors of Cas12 nucleases, which have been engineered to function as RNA-guided DNA endonucleases for genome editing in bacteria and human cells. TnpB nucleases, which are smaller than Cas nucleases, have been engineered for use in genome editing in animal systems, but the feasibility of this approach in plants remained unknown. Here, we obtained stably transformed genome-edited mutants in rice (Oryza sativa) by adapting three recently identified TnpB genome editing vectors, encoding distinct TnpB nucleases (ISAam1, ISDra2, and ISYmu1), for use in plants, demonstrating that the hypercompact TnpB proteins can effectively edit plant genomes. ISDra2 and ISYmu1 precisely edited their target sequences, with no off-target mutations detected, showing that TnpB transposon nucleases are suitable for development into a new genome editing tool for plants. Future modifications improving the genome-editing efficiency of the TnpB system will facilitate plant functional studies and breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00172-6.

Abnormal circadian rhythm of heart rate variability and their association with symptoms in patients with major depressive disorder.

BACKGROUND: Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on short-term HRV, with limited exploration of the 24-h HRV circadian rhythm, despite its ability to comprehensively capture overall HRV distribution and dynamic fluctuations. In this study, we investigated the circadian rhythms of 24-h HRV indices in patients with MDD and their associations with symptom severity. METHODS: We recorded 24-h electrocardiograms in 73 patients with MDD (53 in major depressive episode and 20 in remission period) and 31 healthy controls. An extended cosine model was used to model the circadian rhythm of six HRV indices by five parameters: the mesor, amplitude, duty cycle, curve smoothness, and acrophase. Symptom severity was evaluated using the Hamilton Depression Scale and Hamilton Anxiety Scale. RESULTS: Compared with the control group, patients with MDD had a significantly smaller SampEn mesor, higher HF duty cycle, and lower heart rate (HR) duty cycle. They also had a significantly higher curve smoothness for HR, RMSSD, and HF. The mesor for SampEn, along with the curve smoothness for HR and ln RMSSD, were associated with certain symptoms in patients with MDD. LIMITATIONS: The cross-sectional design and psychiatric treatment of most patients with MDD limited our findings. CONCLUSION: Patients with MDD exhibit abnormal HRV circadian rhythms that are associated with symptoms. Moreover, 24-h ECG monitoring may potentially serve as an adjunct value to objectively evaluate clinical symptoms in these patients.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia. Methods: GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap. Results: We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P < 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported. Conclusions: Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.

Efficient fiber coupling system for simultaneous beam shaping and wavelength combining based on misaligned stepped prism multiplexing.

Due to the substantial contrast in the output beam quality between the two directions of the semiconductor laser, efficiently coupling the beam directly into the fiber is difficult. In this study, an efficient shaping method based on step multiplexing of misaligned step prisms is proposed and investigated systematically. First, multiple laser stacks eliminate dark areas to improve the beam quality through the full utilization of the transmission and reflection surfaces of the misaligned stepped prisms, which also improves the efficiency of the stepped prisms. It also simultaneously realizes laser wavelength combining based on reflective surface multiplexing without affecting the quality of the beam on the premise of improving the output power. Finally, the whole beam shaping system is completed without using cut-transform-rearranging prisms. The method couples four groups of laser stacks into a single fiber with a fiber diameter of 400 µm and a numerical aperture of 0.22. It can be seen from the computer-simulated model outputs that the final fiber output power can reach 2255.4 W and that the system as a whole has a light-to-light translation rate of 88.1%.

Traditional medicine Xianglian pill suppresses high-fat diet-related colorectal cancer via inactivating TLR4/MyD88 by remodeling gut microbiota composition and bile acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown. AIM OF THE STUDY: The primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC. MATERIALS AND METHODS: The protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16S rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a "pseudo-sterile" mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC. RESULTS: XLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression. CONCLUSION: Our findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.

A shifting role of thalamocortical connectivity in the emergence of cortical functional organization.

The cortical patterning principle has been a long-standing question in neuroscience, yet how this translates to macroscale functional specialization in the human brain remains largely unknown. Here we examine age-dependent differences in resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks during early life, using a primarily cross-sectional but also longitudinal approach. We show that thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically influenced axonal projection. This pattern changes in childhood, when connectivity is established with the salience network, while decoupling externally and internally oriented functional systems. A developmental simulation using generative network models corroborated these findings, demonstrating that thalamic connectivity contributes to developing key features of the mature brain, such as functional segregation and the sensory-association axis, especially across 12-18 years of age. Our study suggests that the thalamus plays an important role in functional specialization during development, with potential implications for studying conditions with compromised internal and external processing.

Characterization and correlations of dominant microorganisms and volatile compounds in fermentation process of Yangjiang douchi.

BACKGROUND: Yangjiang douchi (YD) is a traditional fermented soybean product, which is popular in Chinese cuisine for its unique flavor. However, due to its high salt content and unstable flavor, its competitiveness in the international market is gradually weakening. Microorganisms have a key role in the production process of YD because it is a fermented food but the effect of microorganisms on the volatile compounds of YD is also not currently clear. RESULTS: In this paper, aroma compounds and microbial diversity in different fermentation stages of YD were analyzed using gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and IlluminaMiseq system sequencing. A total of 78 aroma-active compounds were detected throughout the fermentation process and they influenced the formation of flavor in YD. Fungi flora were relatively single in YD, and bacteria were rich and varied. A total of 418 species of bacteria were present during fermentation, with unclassified_Staphylococcus, Staphylococcus_kloosii, and Bacillus_velezensis_Bacillus predominating. There were 25 species of fungi at the species level, and Aspergillus minisclerotigenes (OTU 4) played a dominant role in the whole fermentation process. CONCLUSION: Staphylococcus and Bacillus in the bacterial genus were strongly correlated with most flavor compounds detected, and A. minisclerotigenes in the fungi were more relevant to flavor compounds. This research provides a theoretical basis for the enhancement of the flavor of traditional fermented douchi in China. © 2024 Society of Chemical Industry.

The Brain's First "Traffic Map" through Unified Structural and Functional Connectivity (USFC) Modeling.

The brain's white matter connections are thought to provide the structural basis for its functional connections between distant brain regions but how our brain selects the best structural routes for effective functional communications remains poorly understood. In this study, we propose a Unified Structural and Functional Connectivity (USFC) model and use an "economical assumption" to create the brain's first "traffic map" reflecting how frequently each structural connection segment of the brain is used to achieve the global functional communication system. The resulting USFC map highlights regions in the subcortical, default-mode, and salience networks as the most heavily traversed nodes and a midline frontal-caudate-thalamus-posterior cingulate-visual cortex corridor as the backbone of the whole brain connectivity system. Our results further revealed a striking negative association between structural and functional connectivity strengths in routes supporting negative functional connections as well as much higher efficiency metrics in the USFC connectome when compared to structural and functional ones alone. Overall, the proposed USFC model opens up a new window for effective brain connectome modeling and provides a considerable leap forward in brain mapping efforts for a better understanding of the brain's fundamental communication mechanisms.

Integrative analyses identify opportunistic pathogens of patients with lower respiratory tract infections based on metagenomic next-generation sequencing.

Lower respiratory tract infections (LRTIs) represent some of the most globally prevalent and detrimental diseases. Metagenomic next-generation sequencing (mNGS) technology has effectively addressed the requirement for the diagnosis of clinical infectious diseases. This study aimed at identifying and classifying opportunistic pathogens from the respiratory tract-colonizing microflora in LRTI patients using data acquired from mNGS analyses. A retrospective study was performed employing the mNGS data pertaining to the respiratory samples derived from 394 LRTIs patients. Linear discriminant analysis effect size (LEfSe) analysis was conducted to discern the discriminant bacteria. Receiver operating characteristic curves (ROC) were established to demonstrate discriminant bacterial behavior to distinguish colonization from infection. A total of 443 discriminant bacteria were identified and segregated into three cohorts contingent upon their correlation profiles, detection frequency, and relative abundance in order to distinguish pathogens from colonizing microflora. Among them, 119 emerging opportunistic pathogens (cohort 2) occupied an average area under the curve (AUC) of 0.976 for exhibiting the most prominent predictability in distinguishing colonization from infection, 39 were colonizing bacteria (cohort 1, 0.961), and 285 were rare opportunistic pathogens (cohort 3, 0.887). The LTRIs patients appeared modular in the form of cohorts depicting complex microbial co-occurrence networks, reduced diversity, and a high degree of antagonistic interactions in the respiratory tract microbiome. The study findings indicate that therapeutic interventions should target interaction networks rather than individual microbes, providing an innovative perspective for comprehending and combating respiratory infections. Conclusively, this study reports a profile of LRTIs-associated bacterial colonization and opportunistic pathogens in a relatively large-scale cohort, which might serve as a reference panel for the interpretation of mNGS results in clinical practice.

Research on hybrid reservoir scheduling optimization based on improved walrus optimization algorithm with coupling adaptive ε constraint and multi-strategy optimization.

Reservoir flood control scheduling is a challenging optimization task, particularly due to the complexity of various constraints. This paper proposes an innovative algorithm design approach to address this challenge. Combining the basic walrus optimization algorithm with the adaptive ε-constraint method and introducing the SPM chaotic mapping for population initialization, spiral search strategy, and local enhancement search strategy based on Cauchy mutation and reverse learning significantly enhances the algorithm's optimization performance. On this basis, innovate an adaptive approach ε A New Algorithm for Constraints and Multi Strategy Optimization Improvement (ε-IWOA). To validate the performance of the ε-IWOA algorithm, 24 constrained optimization test functions are used to test its optimization capabilities and effectiveness in solving constrained optimization problems. Experimental results demonstrate that the ε-IWOA algorithm exhibits excellent optimization ability and stable performance. Taking the Taolinkou Reservoir, Daheiting Reservoir, and Panjiakou Reservoir in the middle and lower reaches of the Luanhe River Basin as a case study, this paper applies the ε-IWOA algorithm to practical reservoir scheduling problems by constructing a three-reservoir flood control scheduling system with Luanxian as the control point. A comparative analysis is conducted with the ε-WOA, ε-DE and ε-PSO (particle swarm optimization) algorithms.The experimental results indicate that ε-IWOA algorithm performs the best in optimization, with the occupied flood control capacity of the three reservoirs reaching 89.32%, 90.02%, and 80.95%, respectively. The control points in Luan County can reduce the peak by 49%.This provides a practical and effective solution method for reservoir optimization scheduling models. This study offers new ideas and solutions for flood control optimization scheduling of reservoir groups, contributing to the optimization and development of reservoir scheduling work.

Reactive Oxygen Species Activate a Ferritin-Linked TRPV4 Channel under a Static Magnetic Field.

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.

Ca2+ Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Effects of Heat Treatment on the Microstructure and Mechanical Properties of a Dual-Phase High-Entropy Alloy Fabricated via Laser Beam Power Bed Fusion.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via laser beam power bed fusion (LB-PBF), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 °C for 1 h. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also influencing the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 h and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving LB-PBF and heat treatment.

Relationship between ruminative style and adolescent depression.

BACKGROUND: The role of rumination in depression remains controversial. We aimed to establish the ruminative tendency style theory (RTST), discuss the occurrence of depression in adolescents with rumination as the core, and explore the different associations between adolescent ruminative tendency, ruminative style, and depression. METHODS: This study employed an online questionnaire survey of 1110 Chinese adolescents aged 12-17 years, assessing ruminative tendency, ruminative style, stressful life events, depressive state, depressive trait, the Big Five personality traits, and social support. Conditional process analysis was used to test the chain mediation effect with Ruminative Style as a moderator. After screening for the predictor variables, a logistic regression risk prediction model was established and validated internally. RESULTS: The chain mediation effect of ruminative tendency and depressive trait between stressful life events and depressive state was significant, with the indirect effect accounting for 63.4%. Ruminative Style negatively moderated the relationship between Ruminative Tendency and Depressive Trait (ß=-0.053，P＜0.001). The risk prediction model for depressive state showed good calibration and clinical utility. Area under the curve values for the validation and training sets were 0.926 and 0.927, respectively. CONCLUSION: Different associations may exist between adolescent ruminative tendency, ruminative style, and depression, and the proposal of ruminative style is of great significance for intervention in adolescent depression.

Laser therapy decreases oral leukoplakia recurrence and boosts patient comfort: a network meta-analysis and systematic review.

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. CONCLUSION: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.

Structural insights into the catalytic mechanism of the AP endonuclease AtARP.

Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease AtARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in AtARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of AtARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.