Discovery and substrate specificity engineering of nucleotide halogenases.

C2'-halogenation has been recognized as an essential modification to enhance the drug-like properties of nucleotide analogs. The direct C2'-halogenation of the nucleotide 2'-deoxyadenosine-5'-monophosphate (dAMP) has recently been achieved using the Fe(II)/α-ketoglutarate-dependent nucleotide halogenase AdaV. However, the limited substrate scope of this enzyme hampers its broader applications. In this study, we report two halogenases capable of halogenating 2'-deoxyguanosine monophosphate (dGMP), thereby expanding the family of nucleotide halogenases. Computational studies reveal that nucleotide specificity is regulated by the binding pose of the phosphate group. Based on these findings, we successfully engineered the substrate specificity of these halogenases by mutating second-sphere residues. This work expands the toolbox of nucleotide halogenases and provides insights into the regulation mechanism of nucleotide specificity.

Study on the regulation of trophoblast activity by abnormally expressed hsa_circ_0024838/miR-543/HIF1A in patients with gestational diabetes mellitus.

INTRODUCTION: This study aimed to screen circRNAs involved in gestational diabetes mellitus (GDM)-related macrosomia. One differentially expressed circRNA (DEC), hsa_circ_0024838, was further tested for its potential role and mechanism in trophoblasts. METHODS: DECs in GDM were selected through GSE182737 and GSE194119. The targets were predicted for DECs and microRNAs (miRNAs), to complete the construction of the circRNA-miRNA-gene network. Functional annotation and related biological pathway enrichment analysis were performed on the target genes of miRNAs in the network. Subsequently, the expression levels of hsa_circ_0024838, miR-543, and HIF1A mRNA were identified by real-time quantitative real-time PCR (RT-qPCR) in GDM patients. Trophoblast activity was assessed via CCK-8 assay, apoptosis assay, and Matrigel invasion assay. Finally, interactions between miR-543 and either hsa_circ_0024838 or HIF1A were confirmed using dual-luciferase reporter assays. RESULTS: A GDM-related circRNA-miRNA-genes interaction network was constructed, consisting of 35 circRNAs, 46 miRNAs, and 122 target genes. Functional enrichment revealed that the enriched pathways were involved in GDM. Hsa_circ_0024838 and HIF1A mRNA expression levels were upregulated in GDM, while miR-543 expression levels were downregulated. A significant positive correlation between hsa_circ_0024838 and newborn weight was observed. Both hsa_circ_0024838 and HIF1A possessed binding sites for miR-543. Overexpressing hsa_circ_0024838 in high-glucose (HG)-cultured trophoblasts can partially reverse HG-induced reduction in trophoblast cell proliferation/migration and increase apoptosis. But this reversal can be negated by co-transfection with miR-543 mimics. The effects of miR-543 can be counteracted by HIF1A. DISCUSSION: Hsa_circ_0024838 can regulate the expression of HIF1A by interacting with miR-543. This regulates the HIF1A signaling pathway and enhance vitality in trophoblast cells.

Identifying Residues for Substrate Recognition in Human GPAT4 by Molecular Dynamics Simulations.

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in triacylglycerol synthesis. Understanding its substrate recognition mechanism may help to design drugs to regulate the production of glycerol lipids in cells. In this work, we investigate how the native substrate, glycerol-3-phosphate (G3P), and palmitoyl-coenzyme A (CoA) bind to the human GPAT isoform GPAT4 via molecular dynamics simulations (MD). As no experimentally resolved GPAT4 structure is available, the AlphaFold model is employed to construct the GPAT4-substrate complex model. Using another isoform, GPAT1, we demonstrate that once the ligand binding is properly addressed, the AlphaFold complex model can deliver similar results to the experimentally resolved structure in MD simulations. Following the validated protocol of complex construction, we perform MD simulations using the GPAT4-substrate complex. Our simulations reveal that R427 is an important residue in recognizing G3P via a stable salt bridge, but its motion can bring the ligand to different binding hotspots on GPAT4. Such high flexibility can be attributed to the flexible region that exists only on GPAT4 and not on GPAT1. Our study reveals the substrate recognition mechanism of GPAT4 and hence paves the way towards designing GPAT4 inhibitors.

Global evapotranspiration from high-elevation mountains has decreased significantly at a rate of 3.923 %/a over the last 22 years.

Clarifying the responses of human activities and climate change to the water cycle under variable environments is crucial for accurately assessing regional water balance. An analysis of the changes in actual evapotranspiration and its driving factors was conducted in the global high-elevation mountains during the period from 2001 to 2022. Utilizing 18 formulas for calculating evapotranspiration, which are based on comprehensive, temperature, radiation, and mass transfer, and then simulated the variations in reference evapotranspiration. Furthermore, we optimized the ET simulation model based on the most effective simulation results and projected future changes using scenario simulation data. Our findings reveal that: 1) ET at high-elevation mountains has significantly decreased at an average rate of 3.923 %/a, with monthly values ranging from 31.179 to 33.652 mm and an average of 32.646 mm; 2) The radiation-based model of Irmark-Allen is particularly well-suited for simulating ET at high-elevation mountains, with precision analysis and the Taylor diagram confirming its superior simulation performance. After optimizing the model using the method of least squares, the value of R2 before and after the optimization were 0.633 and 0.853, respectively. 3) An upward trend in ET under both SSP245 and SSP585 scenario in future simulation projections. Attribution analysis has identified Vapor Pressure Deficit as the key positive driver influencing the change of ET in global high-elevation mountains. Structural equation modeling further reveals that variations in net radiation and precipitation play a significant role in altering evapotranspiration rates. Meanwhile，The water balance analysis reveals that ET has been declining from 2001 to 2022. This phenomenon can be largely attributed to the substantial decline in vapor pressure deficit, the rise in the Normalized Difference Vegetation Index signifying increased vegetation cover, and the reduction in shallow soil moisture during the same period. These factors collectively explain the notable decrease in ET observed in high-elevation mountains.

Catalytic Asymmetric Cascade Dearomatization of Indoles via a Photoinduced Pd-Catalyzed 1,2-Bisfunctionalization of Butadienes.

Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and a nucleophile represents an emerging and attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in the C-C or C-X bond-formation step have not been solved due to the open-shell process. Herein, we present a cascade asymmetric dearomatization reaction of indoles via photoexcited Pd-catalyzed 1,2-biscarbonfunctionalization of 1,3-butadienes, wherein asymmetric control on both the nucleophile and electrophile part is achieved for the first time in photoinduced bisfunctionalization of butadienes. This method delivers structurally novel chiral spiroindolenines bearing two contiguous stereogenic centers with high diastereomeric ratios (up to >20 : 1 dr) and good to excellent enantiomeric ratios (up to 97 : 3 er). Experimental and computational studies of the mechanism have confirmed a radical pathway involving excited-state palladium catalysis. The alignment and non-covalent interactions between the substrate and the catalyst were found to be essential for stereocontrol.

Mechanical-Force-Induced Non-spontaneous Dehalogenative Deuteration of Aromatic Iodides Enabled by Using Piezoelectric Materials as a Redox Catalyst.

The development of green and efficient deuteration methods is of great significance for various fields such as organic synthesis, analytical chemistry, and medicinal chemistry. Herein, we have developed a dehalogenative deuteration strategy using piezoelectric materials as catalysts in a solid-phase system under ball-milling conditions. This non-spontaneous reaction is induced by mechanical force. D2O can serve as both a deuterium source and an electron donor in the transformation, eliminating the need for additional stoichiometric exogenous reductants. A series of (hetero)aryl iodides can be transformed into deuterated products with high deuterium incorporation. This method not only effectively overcomes existing synthetic challenges but can also be used for deuterium labelling of drug molecules and derivatives. Bioactivity experiments with deuterated drug molecule suggest that the D-ipriflavone enhances the inhibitory effects on osteoclast differentiation of BMDMs in vitro.

Vegetation restoration strategies based on plant water use patterns.

The study on the water source of plants in alpine mountainous is of great significance to optimize the allocation and management of water resources, and can also provide important reference for ecological restoration and protection. However, the controls of water sources for different plants in alpine mountainous region remain poorly understood. Based on the advantages of stable isotope tracer and Bayesian (MixSIAR) model, the water source of plants in Qilian Mountains was quantitatively analyzed. The results showed that the water sources of plants in Qilian Mountain mainly included two parts: direct source and indirect source. The direct source is soil water, which provides most of the water that plants need. The highest contribution of soil water to shrubs was 80 %, followed by trees (73 %) and herbs (72 %). It is worth mentioning that trees mainly use deeper soil water (below 60 cm), shrubs mainly use surface and intermediate soil water (0-60 cm), and herbs mainly use surface soil water (0-40 cm). What is more noteworthy is that indirect sources, such as precipitation, glacier and snow meltwater, and groundwater, are also water sources that cannot be ignored for plant growth in study area. Shrubs and Herbs use more soil water in the range of 40-60 cm, which leads to the possibility of water competition between these two planting types. Therefore, attention should be paid to this phenomenon in the process of vegetation restoration and water resources management. Especially when planting or restoring artificial plants, it is necessary to consider the water use strategy of the two plants to avoid unnecessary water competition and water waste. This is of great significance for ecological stability and sustainable utilization of water resources in the study region.

The effect of freeze-thaw action on the dynamic change of supra-permafrost water sources: A stable isotope perspective.

Due to the continuous degradation (gradual thawing) of permafrost, supra-permafrost water has become an important component of runoff that occurs in cold regions. However, current research has only focused on the amount of water provided by permafrost, and little has been reported regarding the source and formation mechanisms of supra-permafrost water. Due to the difficulty of observation and sampling in cold regions and insufficient data accumulation, model simulations face various difficulties in regard to solving problems related to hydrological processes. Considering the advantages of stable isotope tracer methods in hydrology, the source of supra-permafrost water in Qilian Mountain was analyzed based on 1,840 samples, and the source of supra-permafrost water was determined by end-member mixing analysis (EMMA). Negative line-conditioned excess (lc-excess), lower slope, and particularly the negative intercept of the evaporation line (EL) indicates strong evaporation effects on supra-permafrost water. Remarkably, the evolutionary process, influencing factors, and relationship with other water bodies all indicate that supra-permafrost water is replenished by precipitation, ground ice meltwater, and snow meltwater. The results indicated that from May to October, the contributions of precipitation to the supra-permafrost water were 79%, 83%, 90%, 84%, 87%, and 83%, respectively. Snow meltwater contributed 11%, 13%, 10%, 16%, 11%, and 9%, respectively. Permafrost degradation impacts the water cycle and can increase the minimum monthly runoff and increase groundwater storage. To mitigate the effects of this change, monitoring and early warning systems are essential for detecting signs of permafrost degradation in a timely manner so that appropriate measures can be taken. This may involve the use of remote-sensing technologies, sensor networks, and other methods for real-time monitoring. Establishing mechanisms for sharing information with the relevant departments is crucial. The research results provide scientific and technological support and aid in decision-making to mitigate the negative effects of continuous permafrost degradation in a changing environment.

Long-term organic amendments increase the vulnerability of microbial respiration to environmental changes: Evidence from field and laboratory studies.

Organic amendments can improve soil fertility and microbial diversity, making agroecosystems more resilient to stress. However, it is uncertain whether organic amendments will enhance the functional capacity of soil microbial communities, thereby mitigating fluctuations in microbial respiration caused by environmental changes. Here, we examined the impacts of long-term organic amendments on the dynamics of microbial catabolic capacity (characterized by enzyme activities and carbon source utilization) and microbial respiration, as well as their interrelationships during a period with fluctuating temperature and rainfall in the field. We then subjected the field soil samples to laboratory heating disturbances to further evaluate the importance of microbial catabolic capacity in explaining patterns of microbial respiration. In both field and laboratory experiments, organic amendments tended to increase the stability of microbial catabolic capacity, but significantly increased the vulnerability of microbial respiration to environmental changes. However, the direction and driving factors of microbial respiration affected by environmental changes differed between the field and laboratory experiments. Environmental changes in the field suppressed the promotional effects of organic amendments on microbial respiration mainly through reducing microbial catabolic capacity, while laboratory heating further enhanced microbial respiration mainly due to increased soil resource availability. Together, these findings suggest that increased microbial respiration variations under organic amendments may potentially increase the uncertainty in predicting soil carbon emissions in the scenario of ongoing climate/anthropogenic changes, and highlight the necessity of linking laboratory studies on environmental changes to field conditions.

Advances in the Applications of Extracellular Vesicle for the Treatment of Skin Photoaging: A Comprehensive Review.

Skin photoaging is a complex biological process characterized by the accumulation of oxidative damage and structural changes in the skin, resulting from chronic exposure to ultraviolet (UV) radiation. Despite the growing demand for effective treatments, current therapeutic options for skin photoaging remain limited. However, emerging research has highlighted the potential of extracellular vesicles (EVs), including exosomes, micro-vesicles, apoptotic bodies and liposomes, as promising therapeutic agents in skin rejuvenation. EVs are involved in intercellular communication and can deliver bioactive molecules, including proteins, nucleic acids, and lipids, to recipient cells, thereby influencing various cellular processes. This comprehensive review aims to summarize the current research progress in the application of EVs for the treatment of skin photoaging, including their isolation and characterization methods, roles in skin homeostasis, therapeutic potential and clinical applications for skin photoaging. Additionally, challenges and future directions in EVs-based therapies for skin rejuvenation are discussed.

Field investigation combined with modeling uncovers the ecological heterogeneity of Aedes albopictus habitats for strategically improving systematic management during urbanization.

BACKGROUND: Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. METHODS: A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015-2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. RESULTS: A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. CONCLUSIONS: Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management.

Feasibility and reproducibility of semi-automated longitudinal strain analysis: a comparative study with conventional manual strain analysis.

BACKGROUND: Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific. METHODS: Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation. RESULTS: No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p < 0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p < 0.001). Bland-Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method. CONCLUSIONS: The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement.

Particularity of hydrological processes under heavy ablation based on environmental isotopes in transition zones between endorheic and exorheic basins.

Drastic changes in the cryosphere have a significant impact on the quantity and formation process of water resources in the Qilian Mountains. The present study focused on quantitative evaluation of runoff components and runoff formation processes during strong ablation periods (August), in 2018, 2020, and 2021, in the transition zone between endorheic and exorheic basins in China, based on 1906 stable isotope samples. The results revealed that as the altitude decreased, the contribution of glacier and snow meltwater and permafrost water to runoff decreased, whereas that of the precipitation increased. Precipitation is a major source of river runoff in the Qilian Mountains. Notably, the runoff yield and concentration of rivers that were greatly affected by the cryosphere exhibited the following characteristics: (1) The altitude effect of stable isotopes was not significant and even showed a reverse trend in some rivers. (2) The processes of runoff yield and composition were relatively slow; as such, precipitation, glacier and snow meltwater, and supra-permafrost water were first transformed into groundwater and then supplied runoff to upstream mountainous region. (3) Finally, stable isotope composition in such rivers were similar to those in glaciers and snow meltwater, with small fluctuations. Therefore, the water sources of rivers affected by the cryosphere are more uncertain than those of rivers unaffected by the cryosphere. In future study, a prediction model of extreme precipitation and hydrological events will be developed, and a prediction technology for runoff formation and evolution in glacier snow and permafrost will be developed to integrate short-and long-term forecasts.

High-frequency repetitive transcranial magnetic stimulation protects against cerebral ischemia/reperfusion injury in rats: Involving the mitigation of ferroptosis and inflammation.

BACKGROUND AND AIM: Repetitive transcranial magnetic stimulation (rTMS) has been found to attenuate cerebral ischemia/reperfusion (I/R) injury. However, its effects and mechanism of action have not yet been clarified. It has been reported that cerebral I/R injury is closely associated not only with ferroptosis but also with inflammation. Hence, the current study aimed to investigate whether high-frequency rTMS attenuates middle cerebral artery occlusion (MCAO)-induced cerebral I/R injury and further to elucidate the mediatory role of ferroptosis and inflammation. METHODS: The protective effects of rTMS on experimental cerebral I/R injury were investigated using transient MCAO model rats. Neurological scores and pathological changes of cerebral ischemic cortex were assessed to evaluate the effects of rTMS on cerebral I/R injury. The involvement of ferroptosis and that of inflammation were examined to investigate the mechanism underlying the effects of rTMS. RESULTS: High-frequency rTMS remarkably rescued the MCAO-induced neurological deficits and morphological damage. rTMS treatment also increased the mRNA and protein expression of glutathione-dependent peroxidase 4, decreased the mRNA and protein levels of acyl-CoA synthetase long-chain family member 4 and transferrin receptor in the cortex. Moreover, rTMS administration reduced the cerebrospinal fluid IL-1ß, IL-6, and TNF-α concentrations. CONCLUSION: These findings implicated that high-frequency rTMS alleviates MCAO-induced cerebral I/R injury, and the underlying mechanism could involve the inhibition of ferroptosis and inflammation. Our study identifies rTMS as a promising therapeutic agent for the treatment of cerebral I/R injury. Moreover, the mechanistic insights into ferroptosis and inflammation advance our understanding of it as a potential therapeutic target for diseases beyond cerebral ischemia stroke.

[Spatio-temporal Characteristics of Organic Aggregates and the Driving Factors in Typical Lakes].

Organic aggregates (OA) are the important circulation hub of matter and energy in aquatic ecosystems. However, the comparison studies on OA in lakes with different nutrient levels are limited. In this study, spatio-temporal abundances of OA and OA-attached bacteria (OAB) in oligotrophic Lake Fuxian, mesotrophic Lake Tianmu, middle-eutrophic Lake Taihu, and hyper-eutrophic Lake Xingyun were investigated in different seasons during 2019-2021 using a scanning electron microscope, epi-fluorescence microscope, and flow cytometry. The results showed that:① the annual average abundances of OA in Lake Fuxian, Lake Tianmu, Lake Taihu, and Lake Xingyun were 1.4×104, 7.0×104, 27.7×104, and 16.0×104 ind·mL-1, whereas the annual average abundances of OAB in the four lakes were 0.3×106, 1.9×106, 4.9×106, and 6.2×106 cells·mL-1. The ratios of OAB:total bacteria (TB) in the four lakes were 30%, 31%, 50%, and 38%, respectively. ② OA abundance in summer was significantly higher than that in autumn and winter; however, the ratio of OAB:TB in summer was approximately 26%, which was significantly lower than that in the other three seasons. ③ Lake nutrient status was the most important environmental factor that affected the abundance variations of OA and OAB, accounting for 50% and 68% of the spatio-temporal variations in OA and OAB abundances. ④ Nutrient and organic matters were enriched in OA, especially in Lake Xingyun; the proportions of particle phosphorous, particle nitrogen, and organic matters in this lake were as high as 69%, 59%, and 79%, respectively. Under the circumstance of future climate change and the expansion of lake algal blooms, the effects of algal-originated OA in the degradation of organic matters and nutrient recycling would be increased.

Palladium-Catalyzed Alkyne Hydrocyanation toward Ligand-Controlled Stereodivergent Synthesis of (E)- and (Z)-Trisubstituted Acrylonitriles.

We herein describe a palladium-catalyzed hydrocyanation of propiolamides for the stereodivergent synthesis of trisubstituted acrylonitriles. This synthetic method tolerated various primary, secondary and tertiary propiolamides. The cautious selection of a suitable ligand is essential to the success of this stereodivergent process. Control experiments indicate the intermediacy of E-acrylonitriles, which lead to Z-acrylonitriles via isomerization. The density functional theory calculations suggests that the bidentate ligand L2 enables a feasible cyclometallation/isomerization pathway for the E to Z isomerization, while the monodentate ligand L1 inhibits the isomerization, leading to divergent stereoselectivity. The usefulness of this method can be demonstrated by the readily derivatization of products to give various E- and Z-trisubstituted alkenes. In addition, the E- and Z-acrylonitrile products have also been successfully employed in cycloaddition reactions.

Unveiling the methyl transfer mechanisms in the epigenetic machinery DNMT3A-3 L: A comprehensive study integrating assembly dynamics with catalytic reactions.

In epigenetic mechanisms, DNA methyltransferase 3 alpha (DNMT3A) acts as an initiator for DNA methylation and prevents the downstream genes from expressing. Perturbations of DNMT3A functions may cause uncontrolled gene expression, resulting in pathogenic consequences such as cancers. It is, therefore, vitally important to understand the catalytic process of DNMT3A in its biological macromolecule assembly, viz., heterotetramer: (DNMT3A-3 L)dimer. In this study, we utilized molecular dynamics (MD) simulations, Markov State Models (MSM), and quantum mechanics/molecular mechanics simulations (QM/MM) to investigate the de novo methyl transfer process. We identified the dynamics of the key residues relevant to the insertion of the target cytosine (dC) into the catalytic domain of DNMT3A, and the detailed potential energy surface of the seven-step reaction referring to methyl transfer. Our calculated potential energy barrier (22.51 kcal/mol) approximates the former experimental data (23.12 kcal/mol). The conformational change of the 5-methyl-cytosine (5mC) intermediate was found necessary in forming a four-water chain for the elimination step, which is unique to the other DNMTs. The biological assembly facilitates the creation of such a water chain, and the elimination occurs in an asynchronized mechanism in the two catalytic pockets. We anticipate the findings can enable a better understanding of the general mechanisms of the de novo methyl transfer for fulfilling the key enzymatic functions in epigenetics. And the unique elimination of DNMT3A might ignite novel methods for designing anti-cancer and tumor inhibitors of DNMTs.

Comparisons of the effects of topical anti-scar drugs on post-surgical facial scar formation: a clinical investigation.

OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.