Epigenetic associations of GPNMB rs199347 variant with alcohol consumption in Parkinson's disease.

Introduction: Alcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson's disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the GPNMB gene, with alcohol consumption and methylation upstream of GPNMB. Methods: We retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of GPNMB rs199347 and chronic alcohol consumption (and other potential risk factors) with GPNMB cg17274742 methylation. Results: There was no difference between the distribution of GPNMB rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB rs199347 variant and alcohol consumption (p = 0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (p = 0.0187). Conclusion: Alcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the GPNMB gene, an important neuroinflammatory-related risk gene for PD.

Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals.

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

Single-center retrospective study of the diagnostic value of double-balloon enteroscopy in Meckel's diverticulum with bleeding.

BACKGROUND: The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel's diverticulum (MD) complicated by digestive tract hemorrhage. Moreover, we aimed to evaluate the value of double-balloon enteroscopy (DBE) in MD diagnosis and the prognosis after laparoscopic diverticula resection. AIM: To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding. METHODS: The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations, auxiliary examination, and follow-up after laparoscopic resection of diverticula. RESULTS: (1) Among 84 MD patients complicated with hemorrhage, 77 were male, and 7 were female with an average age of 31.31 ± 10.75 years. The incidence was higher in men than in women of different ages; (2) Among the 84 MD patients, 65 (78.40%) had defecated dark red stools, and 50 (58.80%) had no accompanying symptoms during bleeding, indicating that most MD bleeding appeared a dark red stool without accompanying symptoms; (3) The shock index of 71 patients (85.20%) was < 1, suggesting that the blood loss of most MD patients was less than 20%-30%, and only a few patients had a blood loss of > 30%; (4) The DBE-positive rate was 100% (54/54), 99mTc-pertechnetate-positive scanning rate was 78% (35/45) compared with capsule endoscopy (36%) and small intestine computed tomography (19%). These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding, especially DBE was a highly precise examination method in MD diagnosis; (5) A total of 54 MD patients with hemorrhage underwent DBE examination before surgery. DBE endoscopy revealed many mucosal manifestations including normal appearance, inflammatory changes, ulcerative changes, diverticulum inversion, and nodular hyperplasia, with ulcerative changes being the most common (53.70%). This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding; and (6) Laparoscopic dissection of diverticulae was performed in 76 patients, The patients who underwent postoperative follow-up did not experience any further bleeding. Additionally, follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding. These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis. CONCLUSION: Bleeding associated with MD was predominantly observed in male adolescents, particularly at a young age. DBE was a highly precise examination method in MD diagnosis. Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Microalgae Octapeptide IIAVEAGC Alleviates Oxidative Stress and Neurotoxicity in 6-OHDA-Induced SH-SY5Y Cells by Regulating the Nrf2/HO-1and Jak2/Stat3 Pathways.

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.

Neuroprotection of Truncated Peptide IIAVE from Isochrysis zhanjiangensis: Quantum Chemical, Molecular Docking, and Bioactivity Studies.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile-Ile-Ala-Val-Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.

A literature review of bioactive substances for the treatment of periodontitis: In vitro, in vivo and clinical studies.

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.

BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.

Changes in corneal biomechanics and posterior corneal surface elevation after FS-LASIK.

AIM: To investigate the changes in corneal biomechanics and posterior corneal surface elevation after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: Totally 197 eyes of 100 patients who underwent the FS-LASIK from April 2022 to November 2022 were included. They were divided into three groups according to the ratio of residual corneal stroma thickness/corneal thickness (RCST/CT): Group I (50%≤RCST/CT<55%, 63 eyes of 32 patients), Group II (55%≤RCST/CT<60%, 67 eyes of 34 patients), and Group III (RCST/CT≥60%, 67 eyes of 34 patients). The intraocular pressure (IOP), corneal compensated IOP (IOPcc), corneal hysteresis (CH) and corneal resistance factor (CRF) were measured immediately, 1, and 3mo postoperatively by ocular response analyzer (ORA) and the posterior elevation difference (PED) was measured by Pentacam. RESULTS: After operation, IOP, CH, CRF, and PED were statistically different among the three groups (F=12.99, 31.148, 23.998, all P<0.0001). There was no statistically significant difference in IOPcc among the three groups (F=0.603, P>0.05). The IOP, IOPcc, CH, and CRF were statistical changed after surgery (F=699.635, 104.125, 308.474, 640.145, all P<0.0001). The PED of Group I was significantly higher than that of Group II (P<0.05), and Group II was significantly higher than that of Group III (P<0.05). The PED value of 3mo after surgery decreased in each group compared with 1mo after surgery, but there was no statistical difference (Group I: t=0.82, P=0.41; Group II: t=0.17, P=0.87; Group III: t=1.35, P=0.18). The correlation analysis of corneal biomechanical parameter changes with PED at 1mo and 3mo after surgery showed that ΔIOP, ΔIOPcc, ΔCH, and ΔCRF were not correlated with PED value in three groups (P>0.05). CONCLUSION: The smaller the RCST/CT, the greater effect on corneal biomechanics and posterior surface elevation. There is no correlation between changes in corneal biomechanics and posterior corneal surface elevation in the range of RCST/CT≥50%.

The impact of the chalcogen-substitution element and initial spectroscopic state on excited-state relaxation pathways in nucleobase photosensitizers: a combination of static and dynamic studies.

The substitution of oxygen with chalcogen in carbonyl group(s) of canonical nucleobases gives an impressive triplet generation, enabling their promising applications in medicine and other emerging techniques. The excited-state relaxation S2(ππ*) → S1(nπ*) → T1(ππ*) has been considered the preferred path for triplet generation in these nucleobase derivatives. Here, we demonstrate enhanced quantum efficiency of direct intersystem crossing from S2 to triplet manifold upon substitution with heavier chalcogen elements. The excited-state relaxation dynamics of sulfur/selenium substituted guanines in a vacuum is investigated using a combination of static quantum chemical calculations and on-the-fly excited-state molecular dynamics simulations. We find that in sulfur-substitution the S2 state predominantly decays to the S1 state, while upon selenium-substitution the S2 state deactivation leads to simultaneous population of the S1 and T2,3 states in the same time scale and multi-state quasi-degeneracy region S2/S1/T2,3. Interestingly, the ultrafast deactivation of the spectroscopic S3 state of both studied molecules to the S1 state occurs through a successive S3 → S2 → S1 path involving a multi-state quasi-degeneracy S3/S2/S1. The populated S1 and T2 states will cross the lowest triplet state, and the S1 → T intersystem crossing happens in a multi-state quasi-degeneracy region S1/T2,3/T1 and is accelerated by selenium-substitution. The present study reveals the influence of both the chalcogen substitution element and initial spectroscopic state on the excited-state relaxation mechanism of nucleobase photosensitizers and also highlights the important role of multi-state quasi-degeneracy in mediating the complex relaxation process. These theoretical results provide additional insights into the intrinsic photophysics of nucleobase-based photosensitizers and are helpful for designing novel photo-sensitizers for real applications.

Susceptibility to hypertension based on MTHFR rs1801133 single nucleotide polymorphism and MTHFR promoter methylation.

Background: The aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of MTHFR rs1801133 single nucleotide polymorphism (SNP) and MTHFR promoter methylation with hypertension among Taiwanese adults. Methods: We retrieved data including, MTHFR promoter methylation, MTHFR rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB). Results: The distributions of hypertension and MTHFR promoter methylation quartiles (ß < 0.1338, 0.1338 ≤ ß < 0.1385, 0.1385 ≤ ß < 0.1423, and ß ≥ 0.1423 corresponding to

Risk of gout in Taiwan Biobank participants pertaining to their sex and family history of gout among first-degree relatives.

BACKGROUND: Family history of gout and sex are independently associated with gout. However, there is a paucity of research regarding the joint role of both factors in gout pathogenesis. Therefore, we assessed the independent and combined association of family history of gout and sex with gout. METHODS: Our analysis included 132,311 Taiwan Biobank (TWB)-enrolled individuals comprising 21,159 gout cases and 111,152 controls. We subcategorized the family history of gout as (1) both siblings and parents had gout), (2) only parents had gout, and (3) only siblings had gout. RESULTS: Generally, sex (men compared to women) and family history of gout were independently associated with a higher risk of gout. The odds ratio (OR); 95% confidence interval (CI) was 9.175; 8.801-9.566 for sex, and 2.306; 2.206-2.410 for family history. For the subcategories 'both siblings and had gout,' 'only parents had gout,' and 'only siblings had gout,' the odds ratios (ORs); 95% confidence intervals (CIs) were 4.944; 4.414-5.538, 2.041; 1.927-2.161, and 2.162; 2.012-2.323, respectively. The interaction between sex and family history was significant (p value = 0.0001). After stratification by sex, family history of gout remained significantly associated with a higher risk of gout in both sexes, even though the odds ratios were higher in men. For the subcategories 'both siblings and parents had gout,' 'only parent had gout,' and 'only siblings had gout,' the corresponding ORs; 95% CIs were 6.279; 5.243-7.520, 2.211; 2.062-2.371, and 2.148; 1.955-2.361 in men and 4.199; 3.566-4.945, 1.827; 1.640-2.035, and 2.093; 1.876-2.336 in women. After integrating sex and family history (reference: women with no family history), the highest risk of gout was observed in men who had at least one parent and sibling with a history of gout (OR; 95% CI 55.774; 46.360-67.101). CONCLUSION: Sex and family history of gout were independently and interactively associated with gout. Sex-wise, men had a higher risk of gout than women. Family history was associated with a higher risk of gout in both sexes, but men had a higher risk. Notably, men having both siblings and parents with gout had the highest risk of gout.

Epigenetic regulation of Parkinson's disease risk variant GPNMB cg17274742 methylation by sex and exercise from Taiwan Biobank.

Background: Parkinson's disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals. Methods: We analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension. Results: Our results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (ß = -0.00242; p = 0.0026), but not in females (ß = -0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (ß = -0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078). Conclusion: This study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.

One-year clinical efficacy evaluation of selective corneal wavefront aberration-guided FS-LASIK correction in patients with high myopia.

AIM: To evaluate the effectiveness, safety, predictability, precision and changes of higher-order aberrations (HOAs) on corneal front surface of selective corneal wavefront aberration-guided femtosecond laser-assisted in situ keratomileusis (CW-FS-LASIK) in patients with high myopia 1-year postoperatively. METHODS: Totally 74 eyes of 37 patients with high myopia or myopic astigmatism in both the eyes who underwent the CW-FS-LASIK procedure in Xi'an Gaoxin Hospital from January 2021 to June 2021 were included. The changes of uncorrected distance visual acuity (UDVA), best corrected visual acuity (BCVA), spherical equivalent refraction (SER), astigmatism, HOAs and Strehl ratio (SR) on the anterior surface of the cornea after 1y of the surgery were analyzed. RESULTS: At postoperative 1y, the UDVA (logMAR) of 74 eyes (100%) reached 0 or better, including 0 in 8 eyes (10.81%), -0.1 in 45 eyes (60.81%), and -0.2 in 21 eyes (28.38%). The effectiveness index was 1.29±0.134. There was no decrease in postoperative BCVA compared with preoperative BCVA in all patients. Postoperative BCVA was the same in 44 eyes (59.46%) as preoperative BCVA, increased by 1 line in 23 eyes (31.08%) and increased by 2 lines in 7 eyes (9.46%) compared with preoperative BCVA. The safety index was 1.11±0.159. The estimated corrected SER before surgery was (-7.76±1.21) D, and the actual corrected SER was (-7.83±1.25) D (Y=0.9811X+0.2156, R2=0.9084). There was a high correlation between the estimated corrected SER and the actual corrected SER. The postoperative SER in 74 eyes (100%) was within ±0.75 D. The postoperative astigmatism of all was within -0.75 D to 0. Root mean square (RMS) HOAs of spherical aberration and SR within 5 mm of the corneal front surface were all increased compared with those before operation (P<0.01). The total coma, horizontal coma and vertical coma were all decreased compared with those before operation (P<0.01). There was no statistically significant difference in horizontal trefoil and vertical trefoil compared with preoperative ones (P>0.05). CONCLUSION: Selective CW-FS-LASIK for correction of high myopia is effective, safe, predictive, and accurate. For patients with preoperative RMS HOAs over 0.25 defocus equivalent, postoperative coma aberration can be significantly reduced, and SR value can be increased, thus corneal imaging quality can be improved.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Plastic wastes and surface antibiotic resistance genes pollution in mangrove environments.

Mangroves are located at the intersection of land and sea and are also heavily affected by plastic wastes. Biofilms of plastic wastes in mangroves are reservoirs for antibiotic resistance genes (ARGs). In this study, plastic wastes and ARG pollution were investigated from three typical mangrove areas in Zhanjiang, South China. Transparent was the dominant colors of plastic wastes in three mangroves. Fragment and film shape accounted for 57.73-88.23% of plastic waste samples in mangroves. In addition, 39.50% of plastic wastes in protected area mangroves are PS. The metagenomic results shows that the 175 ARGs were found on plastic wastes of the three mangroves, the abundance accounting for 91.11% of the total ARGs. The abundance of Vibrio accounted for 2.31% of the total bacteria genera in aquaculture pond area mangrove. Correlation analysis shows that a microbe can carry multiple ARGs that may improve resistance to antibiotics. Microbes are the potential hosts of most ARGs, suggesting that ARGs can be transmitted by microbes. Because the mangroves are closely related to human activities and the high abundance of ARGs on plastic increases the ecological risks, people should improve plastic waste management and prevent the spread of ARGs by reducing plastic pollution.

Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

miR-27a-3p relieves heat stress-induced mitochondrial damage and aberrant milk protein synthesis through MEK/ERK pathway in BMECs.

With global warming, heat stress has become a primary factor that compromises the health and milk quality of dairy cows. Here, we investigated the function and underlying regulatory mechanism of miR-27a-3p in bovine mammary epithelial cells (BMECs) under heat-stress conditions. The current study showed that miR-27a-3p could prevent heat stress-induced BMEC oxidative stress and mitochondrial damage by regulating the balance between mitochondrial fission and fusion processes. Importantly, we found that miR-27a-3p could increase cell proliferation under heat stress conditions by regulating the MEK/ERK pathway and cyclin D1/E1. Interestingly, miR-27a-3p is also involved in the regulation of milk protein synthesis-related protein expression, such as CSN2 and ELF5. Inhibition of the MEK/ERK signaling pathway by AZD6244 blocked the regulatory function of miR-27a-3p in cell proliferation and milk protein synthesis in BMECs under heat stress conditions. Our findings demonstrated that miR-27a-3p protects BMECs from heat stress-induced oxidative stress and mitochondrial damage through the MEK/ERK pathway, thereby promoting BMECs proliferation and lactation in dairy cows. The potential regulatory mechanism of miR-27a-3p in attenuating heat stress-induced apoptosis and lactation defect in BMECs.