"Severe blepharoptosis correction with the fixation of levator complex and conjoint fascial sheath: 12 Years of Experience in a Single Center."

BACKGROUND: The correction of severe blepharoptosis is one of the most challenging surgeries in plastic surgery. This study introduces a novel self-reinforced fixation technique combining the levator complex with conjoint fascial sheath for the correction of severe blepharoptosis and reviews the postoperative results over the preceding 12 years. METHODS: This retrospective review included all patients who underwent self-reinforced fixation with or without conjoint fascial sheath at the authors' center between 2010 and 2022. The clinical data of the two groups were collected and evaluated. RESULTS: All patients were followed up for 6 months to 8 years postoperatively. The mean postoperative MRD1 and LF increased significantly in both groups. Sufficient correction of ptosis was achieved in 32 (65.31%) and 84 (81.56%) eyelids in Groups I and II, respectively. The mean eyelid lagophthalmos was 1.27± 0.91 mm and 0.85 ± 0.89 mm in Groups I and II, respectively. The most common complication was undercorrection of ptosis, which was observed in 14 eyelids (28.57%) and 15 eyelids (14.56%) in Groups I and II, respectively. CONCLUSIONS: The self-reinforced fixation technique was effective in correcting severe congenital ptosis in Chinese patients. The clinical effect was consistent in the long-term follow-up cases, and the recurrence rate was low. Thus, this technique can enhance the strength of the levator muscle and maintain appropriate elasticity of eye closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae.

Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-rearing industry. Whole-transcriptome analyses have revealed non-coding RNAs and their regulatory networks in N. bombycis infected embryos and larvae. However, transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae remains unclear. Here, we simultaneously compared the transcriptomes of N. bombycis and its host B. mori embryos of 5-day and larvae of 1-, 5- and 10-day during congenital infection. For the transcriptome of N. bombycis, a comparison of parasite expression patterns between congenital-infected embryos and larva showed most genes related to parasite central carbon metabolism were down-regulated in larvae during infection, whereas the majority of genes involved in parasite proliferation and growth were up-regulated. Interestingly, a large number of distinct or shared differentially expressed genes (DEGs) were revealed by the Venn diagram and heat map, many of them were connected to infection related factors such as Ricin B lectin, spore wall protein, polar tube protein, and polysaccharide deacetylase. For the transcriptome of B. mori infected with N. bombycis, beyond numerous DEGs related to DNA replication and repair, mRNA surveillance pathway, RNA transport, protein biosynthesis, and proteolysis, with the progression of infection, a large number of DEGs related to immune and infection pathways, including phagocytosis, apoptosis, TNF, Toll-like receptor, NF-kappa B, Fc epsilon RI, and some diseases, were successively identified. In contrast, most genes associated with the insulin signaling pathway, 2-oxacarboxylic acid metabolism, amino acid biosynthesis, and lipid metabolisms were up-regulated in larvae compared to those in embryos. Furthermore, dozens of distinct and three shared DEGs that were involved in the epigenetic regulations, such as polycomb, histone-lysine-specific demethylases, and histone-lysine-N-methyltransferases, were identified via the Venn diagram and heat maps. Notably, many DEGs of host and parasite associated with lipid-related metabolisms were verified by RT-qPCR. Taken together, simultaneous transcriptomic analyses of both host and parasite genes lead to a better understanding of changes in the microsporidia proliferation and host responses in embryos and larvae in N. bombycis congenital infection.

Associations of Combined Exposure to Metabolic and Inflammatory Indicators with Thyroid Nodules in Adults: A Nested Case-Control Study.

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice.

Background: Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer's disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly. Methods: In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia. Results: The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells. Conclusion: Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway.

We evaluated the expression profiles of differentially expressed miRNAs (DEmiRNAs) involved in human fetal skin development via high-throughput sequencing to explore the expression difference and the regulatory role of miRNA in different stages of fetal skin development. Analysis of expression profiles of miRNAs involved collecting embryo samples via high-throughput sequencing, then bioinformatics analyses were performed to validate DEmiRNAs. A total of 363 miRNAs were differentially expressed during the early and mid-pregnancy of development, and upregulated DEmiRNAs were mainly concentrated in the let-7 family. The transfection of let-7b-5p slowed down HaCaT cell proliferation and promoted apoptosis, as evidenced by the cell counting kit-8 assay, quantitative real-time polymerase chain reaction, and flow cytometry. The double luciferin reporter assay also confirmed let-7b-5p and ΔNp63 downregulation through the combination with the 3'-untranslated region of ΔNp63. Moreover, treatment with a let-7b-5p inhibitor upregulated ΔNp63 and activated the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. The let-7b-5p caused a converse effect on HaCaT cells because of Np63 upregulation. Let-7b-5p regulates skin development by targeting ΔNp63 via PI3K-AKT signaling, contributing to future studies on skin development and clinical scar-free healing.

In-situ investigation of supercooling behaviour during high-pressure shift freezing of pure water and sucrose solution.

Supercooling is a main controllable factor for the fundamental understanding the high-pressure shift freezing (HPSF). In the study, a self-developed device based on the diamond anvil cell (DAC) and confocal Raman microscopy was utilized to realize an in-situ investigation of supercooling behaviour during HPSF of the pure water and sucrose solution. The spectra were used to determine the freezing point which is shown as a spectral phase marker (SD). The hydrogen bond strengths of water and sucrose solution under supercooling states were estimated by peak position and peak area ratio of sub-peaks. The results showed that the OH stretching bands had redshift under supercooling states. Moreover, the addition of sucrose molecules could strengthen the hydrogen bonding strength of water molecules under supercooling states. Thus, the DAC combined with Raman spectroscopy could be considered a novel strategy for a deep understanding of the supercooling behaviour during HPSF.

In Situ Formed Robust Solid Electrolyte Interphase with Organic-Inorganic Hybrid Layer for Stable Zn Metal Anode.

Stabilizing the Zn anode/electrolyte interface is critical for advancing aqueous zinc ion storage technologies. Addressing this challenge helps minimize parasitic reactions and controls the formation of Zn dendrites, which is fundamental to achieving highly reversible Zn electrochemistry. In this study, 2% by volume of dimethyl sulfoxide (DMSO) is introduced into the baseline zinc sulfate (ZS) electrolyte, which acts as an efficient regulator to form a robust solid-electrolyte interphase (SEI) on the Zn anode. This innovative approach enables uniform Zn deposition and does not substantially modify the Zn2+ solvation structure. The Zn||Zn symmetric cell exhibits an extended cycle life of nearly one calendar year (>8500 h) at a current density of 0.5 mA cm-2 and an areal capacity of 0.5 mAh cm-2. Impressive full cell performance can be achieved. Specifically, the Zn||VS2 full cell achieves an areal capacity of 1.7 mAh cm-2, with a superior negative-to-positive capacity ratio of 2.5, and an electrolyte-to-capacity ratio of 101.4 µL mAh-1, displaying remarkable stability over 1000 cycles under a high mass loading of 11.0 mg cm-2 without significant degradation. This innovative approach in electrolyte engineering provides a new perspective on in situ SEI design and furthers the understanding of Zn anode stabilization.

Facial adult female acne in China: An analysis based on artificial intelligence over one million.

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.

Linoelaidic acid gavage has more severe consequences on triglycerides accumulation, inflammation and intestinal microbiota in mice than elaidic acid.

This work aims to study the effects of oral gavage (0.2 mg/g body weight) of elaidic acid (C18:1-9 t, EA) and linoelaidic acid (C18:2-9 t,12 t, LEA) on lipid metabolism, inflammation and gut homeostasis of mice. Results showed that both EA and LEA gavage significantly increased LDL-c, TC and oxidative stress levels in the liver and serum and may stimulate liver inflammation via NF-κB and MAPK signaling pathway. Compared with EA, LEA gavage significantly promoted TAG accumulation and inflammatory signaling. Serum lipidomics revealed that LEA intake significantly increased the concentration of ∼50 TAGs, while EA gavage primarily caused significant decreases in several SMs. 16S rRNA demonstrated that LEA ingestion markedly changed fecal microbiota by enriching Lactobacillus (phylum Firmicutes), however, EA treatment did not affect it. Overall, LEA gavage has more severe consequences on TAG accumulation, inflammation and microbial structure than EA, highlighting that the number of trans double bonds affects these processes.

The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.

Cerebral revascularization for complex vertebrobasilar artery dissecting aneurysms.

Vertebrobasilar artery dissecting aneurysms (VBDAs) are the most surgically challenging type of aneurysm. Cerebral revascularization is the ultimate treatment for complex VBDAs. We retrospectively analysed the characteristics, surgical outcomes and follow-up data of 21 patients who underwent cerebral revascularization to treat complex VBDAs from 2015 to 2022. According to the location of the aneurysm and the anatomic relationship between the VBDA and the PICA, VBDA patients were classified into four groups: aneurysms located at the VA with PICA involvement (10 patients), aneurysms located at the VA without PICA involvement (1 patient), aneurysms located at the basilar apex segment (1 patient) and aneurysms located at the basilar trunk segment (9 patients). A surgical algorithm for complex VBDAs was determined primarily by the location of the aneurysm, the status of the aneurysm and the ability of retrograde blood flow to reach the proximal vertebrobasilar artery. Surgical modalities for patients with aneurysms in the VA with PICA involvement included low-flow (OA-PICA) bypasses with aneurysm trapping, aneurysm excision or reconstructive clip in 8 patients and STA-PCA bypass combined with PICA preservation and aneurysm trapping in 2 patients. In patients with aneurysms in the VA without PICA involvement, aneurysm excision was performed without cerebral bypass. In patients with aneurysms in the basilar apex segment, high-flow bypass (ECA-RA-P2) with aneurysm trapping was performed. In patients with aneurysms in the basilar trunk segment, surgical modalities included high-flow bypasses (ECA-RA-P2 and LVA-RA-P2) with aneurysm trapping or proximal occlusion in 6 patients, ECA-RA-P2 bypass with partial proximal occlusion in 1 patient, ECA-RA-P2 bypass alone in 1 patient, and STA-PCA bypass with R-VA narrowing in 1 patient. Of the 21 patients, 20 experienced clinical improvement or no change, and 17 of 21 patients achieved favourable functional outcomes (mRS ≤ 2). However, one patient died of infarction and respiratory failure postoperatively. Aneurysms were completely obliterated in 13 patients, shrank in 5 patients and stabilized in 2 patients. The median follow-up period was 32.5 months. During the follow-up period, all bypasses were patent, and further clinical improvement was observed in 11 patients. Cerebral revascularization appears to be safe and effective for the treatment of complex VBDAs, and cerebral revascularization could act as a complementary treatment strategy.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors.

Objective: Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods: Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples. Results: In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. "Pyruvate" "alpha-linolenic acid" and "2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine" are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion: Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

3D printable strong and tough composite organo-hydrogels inspired by natural hierarchical composite design principles.

Fabrication of composite hydrogels can effectively enhance the mechanical and functional properties of conventional hydrogels. While ceramic reinforcement is common in many hard biological tissues, ceramic-reinforced hydrogels lack a similar natural prototype for bioinspiration. This raises a key question: How can we still attain bioinspired mechanical mechanisms in composite hydrogels without mimicking a specific composition and structure? Abstracting the hierarchical composite design principles of natural materials, this study proposes a hierarchical fabrication strategy for ceramic-reinforced organo-hydrogels, featuring (1) aligned ceramic platelets through direct-ink-write printing, (2) poly(vinyl alcohol) organo-hydrogel matrix reinforced by solution substitution, and (3) silane-treated platelet-matrix interfaces. Unit filaments are further printed into a selection of bioinspired macro-architectures, leading to high stiffness, strength, and toughness (fracture energy up to 31.1 kJ/m2), achieved through synergistic multi-scale energy dissipation. The materials also exhibit wide operation tolerance and electrical conductivity for flexible electronics in mechanically demanding conditions. Hence, this study demonstrates a model strategy that extends the fundamental design principles of natural materials to fabricate composite hydrogels with synergistic mechanical and functional enhancement.

Imbibition Characteristics and Influencing Factors of the Fracturing Fluid in a Tight Sandstone Reservoir.

The strong reservoir heterogeneity and complex microscopic pore structure in the Linxing area make it prone to water block damage during imbibition development. In order to explore the influence of reservoir microscopic characteristics on imbibition efficiency, taking the tight sandstone gas reservoir in the Linxing area of Ordos Basin as an example, the heterogeneity of the tight sandstone reservoir in the study area is characterized in terms of physical and chemical characteristics as well as the microscopic pore structure. Using nuclear magnetic resonance, high-pressure mercury pressure, and other testing methods, spontaneous seepage experiments in real sandstone were carried out to study the distribution law of different pore structures and seepage characteristics at different times and to systematically evaluate the microscopic pore characteristics of dense sandstone reservoirs and the factors affecting seepage and suction. The results show that due to the strong microscopic heterogeneity of tight sandstone, the macroscopic properties cannot directly reflect the microscopic characteristics, and the response to imbibition efficiency is stronger. The pore size is the main controlling factor affecting imbibition, and the contribution rate of the micropore and mesopore mainstream pore size spaces is higher than that of the macropore. Micropores provide imbibition power, and mesopores provide an imbibition interval. High-porosity and high permeability reservoirs are more conducive to imbibition replacement. The intercrystalline pores have a great influence on the imbibition efficiency, and the influence of intergranular pores and dissolution pores on the imbibition cannot be underestimated. The smaller the relative sorting coefficient, interfacial tension, and contact angle, the better the imbibition effect of fracturing fluid. Research results have theoretical guiding significance for spontaneous imbibition to improve oil recovery.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Exploring transvaginal sonographic characteristics of the levator ani muscle in women with postpartum pelvic floor myofascial pain.

BACKGROUND: Pelvic floor myofascial pain is one of the pelvic floor dysfunction diseases disturbing women after delivery. There is a lack of objective standardization for the diagnosis of pelvic floor myofascial pain due to the various symptoms and the dependence on the palpating evaluation. Ultrasound imaging has the advantages of safety, simplicity, economy and high resolution, which makes it an ideal tool for the assistant diagnosis of pelvic floor myofascial pain and evaluation after treatment. METHODS: This is a retrospective case-control study including women accepting evaluation of pelvic floor function at 6 weeks to 1 year postpartum. They were divided into pelvic floor myofascial pain group and normal control group. A BCL 10-5 biplane transducer was applied to observed their puborectalis. The length, minimum width, area, deficiency, deficiency length, deficiency width, deficiency area, rate of deficiency area, local thickening,angle between the tendinous arch of levator ani muscle and puborectalis of corresponding puborectalis in different groups were observed and measured. RESULTS: A total of 220 postpartum women participated in the study, with 77 in the pelvic floor myofascial pain group and 143 in the normal control group. The Intraclass correlation coefficient value was over 0.750, and Kappa ranged from 0.600 to 0.800. puborectalis deficiency (adjusted odds ratio = 11.625, 95% confidence interval = 4.557-29.658) and focal thickening (adjusted odds ratio = 16.891, 95% confidence interval = 1.819-156.805) were significantly associated with higher odds of having postpartum pelvic floor myofascial pain. Grayscale or the angle between the arch tendineus levator ani and puborectalis measurements on the pain side tended to be smaller than on the non-pain side in patients with unilateral puborectalis or iliococcygeus pain (P < 0.05). CONCLUSIONS: This study demonstrated that transvaginal ultrasound was a potentially efficient technique for evaluating postpartum pelvic floor myofascial pain due to its ability to assess various sonographic characteristics of the levator ani muscles.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Deciphering the spatial heterogeneity of groundwater arsenic in quaternary aquifers of the Central Yangtze River Basin.

Significant spatial variability of groundwater arsenic (As) concentrations in South/Southeast Asia is closely associated with sedimentogenesis and biogeochemical cycling processes. However, the role of fine-scale differences in biogeochemical processes under similar sedimentological environments in controlling the spatial heterogeneity of groundwater As concentrations is poorly understood. Within the central Yangtze Basin, dissolved organic matter (DOM) and microbial functional communities in the groundwater and solid-phase As-Fe speciation in Jianghan Plain (JHP) and Jiangbei Plain (JBP) were compared to reveal mechanisms related to the spatial heterogeneity of groundwater As concentration. The optical signatures of DOM showed that low molecular terrestrial fulvic-like with highly humified was predominant in the groundwater of JHP, while terrestrial humic-like and microbial humic-like with high molecular weight were predominant in the groundwater of JBP. The inorganic carbon isotope, microbial functional communities, and solid-phase As-Fe speciation suggest that the primary process controlling As accumulation in JHP groundwater system is the degradation of highly humified OM by methanogens, which drive the reductive dissolution of amorphous iron oxides. While in JBP groundwater systems, anaerobic methane-oxidizing microorganisms (AOM) coupled with fermentative bacteria, iron reduction bacteria (IRB), and sulfate reduction bacteria (SRB) utilize low molecular weight DOM degradation to drive biotic/abiotic reduction of Fe oxides, further facilitating the formation of carbonate associated Fe and crystalline Fe oxides, resulting in As release into groundwater. Different biogeochemical cycling processes determine the evolution of As-enriched aquifer systems, and the coupling of multiple processes involving organic matter transformation­iron cycling­sulfur cycling-methane cycling leads to heterogeneity in the spatial distribution of As concentrations in groundwater. These findings provide new perspectives to decipher the spatial variability of As concentrations in groundwater.

CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway.

Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.