Susceptibility to eye diseases in relation to age and kidney failure among Taiwanese adults.

BACKGROUND: The kidney and eyes share common pathways and are thought to be closely connected. Chronic kidney disease and major eye diseases, such as cataract and glaucoma, are strongly associated with age. However, further investigation is needed to understand the joint impact of age and kidney diseases on eye diseases. In this study, we assessed the risk of eye diseases in relation to age and kidney failure in Taiwanese adults. METHODS: Our study included 127,561 cancer-free volunteers aged 30 to 70 years who participated in the Taiwan Biobank (TWB) project from 2008 to 2020. Information on the main exposures (kidney failure and age) and the outcome (eye diseases, including glaucoma, cataract, xerophthalmia, and retinal detachment) was collected through questionnaires. RESULTS: In general, kidney failure and older age were independently associated with a higher risk of eye, particularly cataract and retinal detachment: prevalence odds ratio (POR); 95% confidence interval (CI) = 2.480; 1.635-3.761 for cataract and 3.885; 1.968-7.666 for retinal detachment. A significant interaction between kidney failure and age on cataract was observed (p-value = 0.0002). Age-stratified analysis revealed a higher risk of cataract among patients with kidney failure aged below 50 (POR = 6.534; 95% CI = 2.493-17.124) and between 50 and 60 years (POR = 3.957; 95%CI = 1.986-7.881). Combining kidney failure and age (reference: no kidney failure and age < 50 years), kidney failure in all age groups was associated with a higher risk of cataract. The PORs; 95% CIs were 10.725; 4.227-27.211 for patients below 50 years, 28.487; 14.270-56.866 for those aged 50-60 years, and 43.183; 24.434-72.824 for those > 60 years. Combining cataract and age (reference: no cataract and age < 50 years), patients below 50 years had the highest risk of kidney failure (POR; 95% CI = 9.510; 3.722-24.297). CONCLUSIONS: Our study suggests that age and kidney failure may jointly contribute to eye diseases, particularly cataract. The association between cataract and kidney failure could be bidirectional, especially in individuals below 50 years. This significant bidirectional relationship underscores the need for screening patients with cataract for kidney failure and vice versa, particularly in younger adults.

Risk of HBV infection among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan.

BACKGROUND: In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. METHODS: Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. RESULTS: The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13-0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34-1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40-1.55 for those born before July 1986 but declined to 1.15, 1.02-1.29 for those born after July 1986. CONCLUSIONS: The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

PM2.5 exposure and DLEC1 promoter methylation in Taiwan Biobank participants.

BACKGROUND: Particulate matter (PM) < 2.5 µm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5 and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise. METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5 data from the Air Quality Monitoring Database (AQMD) and estimated participants' exposure using residential addresses. RESULTS: DLEC1 methylation and PM2.5 were positively associated: beta coefficient (ß) = 0.114 × 10-3; p value = 0.046. The test for interaction between exercise and PM2.5 on DLEC1 methylation was significant (p value = 0.036). After stratification by exercise habits, PM2.5 and DLEC1 methylation remained significantly associated only among those who exercised regularly (ß = 0.237 × 10-3; p value = 0.007). PM2.5 quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5 < 27.37 µg/m3 (ß = - 5.280 × 10-3; p value = 0.009). After combining exercise habits and PM2.5 quartiles, one stratum (i.e., regular exercise and PM2.5 < 27.37 µg/m3) was inversely associated with DLEC1 methylation (ß = -5.160 × 10-3, p value = 0.007). CONCLUSIONS: We found significant positive associations between PM2.5 and DLEC1 promoter methylation. Regular exercise at PM2.5 < 27.37 µg/m3 seemingly regulated DLEC1 promoter methylation.

Vegetarian Diets along with Regular Exercise: Impact on High-Density Lipoprotein Cholesterol Levels among Taiwanese Adults.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30-70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (ß = -5.705; p = 0.001) followed by lacto-ovo vegetarians (ß = -3.900; p < 0.001) and former vegetarians (ß = -0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the ß-value was -13.984 for strict vegetarians, -4.419 for lacto-ovo vegetarians, and -1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Functional Investigations of p53 Acetylation Enabled by Heterobifunctional Molecules.

Post-translational modifications (PTMs) dynamically regulate the critical stress response and tumor suppressive functions of p53. Among these, acetylation events mediated by multiple acetyltransferases lead to differential target gene activation and subsequent cell fate. However, our understanding of these events is incomplete due to, in part, the inability to selectively and dynamically control p53 acetylation. We recently developed a heterobifunctional small molecule system, AceTAG, to direct the acetyltransferase p300/CBP for targeted protein acetylation in cells. Here, we expand AceTAG to leverage the acetyltransferase PCAF/GCN5 and apply these tools to investigate the functional consequences of targeted p53 acetylation in human cancer cells. We demonstrate that the recruitment of p300/CBP or PCAF/GCN5 to p53 results in distinct acetylation events and differentiated transcriptional activities. Further, we show that chemically induced acetylation of multiple hotspot p53 mutants results in increased stabilization and enhancement of transcriptional activity. Collectively, these studies demonstrate the utility of AceTAG for functional investigations of protein acetylation.

Variations in high density cholesterol levels based on apolipoprotein E variant and exercise type.

In various cross-sectional and longitudinal studies, exercise has been associated with cardiometabolic outcomes, including high-density lipoprotein (HDL) cholesterol. Exercise-induced changes in HDL cholesterol seem to be affected by genetic polymorphisms. In this study, we examined whether variant APOE rs7412 is involved in the association between HDL cholesterol and exercise. From adults assessed in Taiwan Biobank (TWB) between 2008 and 2019, we analyzed data from 57,638 normolipidemic subjects. To examine the association between exercise, APOE rs7412, and HDL cholesterol, a multiple linear regression model was used. A higher HDL was associated with both aerobic exercise (regression coefficient [mg/dL] beta- (ß), 1.112; 95% confidence interval (CI); 0.903-1.322) and resistance exercise (ß, 2.530; 95% CI, 2.093-2.966). In comparison with the APOE rs7412-CC genotype, the ß was 2.589 (95% CI, 2.329-2.848) among those with the CT + TT genotype. Compared to adults who had the CC genotype and did not exercise (the CC/no exercise group), the ß-coefficient determined for the different genotype and exercise groups was 1.135 (95% CI, 0.911-1.359) for the CC genotype and aerobic exercise group, 2.753 (95% CI, 2.283-3.322) for the CC genotype and resistance exercise group, 2.705 (95% CI, 2.390-3.020) for the CT + TT genotype and no exercise group, 3.682 (95% CI, 3.218-4.146) for the CT + TT genotype and aerobic exercise group, and 3.855 (95% CI, 2.727-4.982) for the CT + TT genotype and resistance exercise group, respectively. This study demonstrates that self-reported aerobic and resistance exercise both raised HDL levels, yet resistance exercise was associated with a greater increase, particularly among Taiwanese subjects carrying the APOE rs7412-CT+TT genotype.

In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design.

The COVID-19 pandemic has had a widespread impact on a global scale, and the evolution of considerable dominants has already taken place. Some variants contained certain key mutations located on the receptor binding domain (RBD) of spike protein, such as E484K and N501Y. It is increasingly worrying that these variants could impair the efficacy of current vaccines or therapies. Therefore, analyzing and predicting the high-risk mutations of SARS-CoV-2 spike glycoprotein is crucial to design future vaccines against the different variants. In this work, we proposed an in silico approach, immune-escaping score (IES), to predict high-risk immune-escaping hot spots on the receptor-binding domain (RBD), implemented through integrated delta binding free energy measured by computational mutagenesis of spike-antibody complexes and mutation frequency calculated from viral genome sequencing data. We identified 23 potentially immune-escaping mutations on the RBD by using IES, nine of which occurred in omicron variants (R346K, K417N, N440K, L452Q, L452R, S477N, T478K, F490S, and N501Y), despite our dataset being curated before the omicron first appeared. The highest immune-escaping score (IES = 1) was found for E484K, which agrees with recent studies stating that the mutation significantly reduced the efficacy of neutralization antibodies. Furthermore, our predicted delta binding free energy and IES show a high correlation with high-throughput deep mutational scanning data (Pearson's r = 0.70) and experimentally measured neutralization titers data (mean Pearson's r = -0.80). In summary, our work presents a new method to identify the potentially immune-escaping mutations on the RBD and provides valuable insights into future COVID-19 vaccine design.

Acupuncture for ventilator-dependent patients at a hospital-based respiratory care center: A randomized controlled trial.

Background: In intensive care units, mechanical ventilation is an important therapy to help patients with dyspnea. However, long-term ventilator dependence would consume huge medical resources and increase the risk of morbidity and mortality. The aim of the study was to examine the efficacy of the acupuncture combined with western medical care on ventilator parameters in ventilator-dependent patients. Methods: In this clinical trial, 80 ventilator-dependent patients aged 20 to 80 years old were randomly assigned to acupuncture group and control group in the respiratory care center (RCC) of Changhua Christian Hospital. Besides regular medical care and therapy, participants in the acupuncture group received acupuncture therapy at the same 17 acu-points for 20 minutes once a day, a total of 12 sessions. The ventilator parameters were recorded to evaluate the respiratory efficiency for all participants. The primary outcome was rapid shallow breathing index (RSBI), and secondary outcomes were respiratory rate (RR), tidal volume (TV) and ventilation per minute (MV). Results: Though there was no significant difference in the parameter between the acupuncture group and the control group, we found the trend of decreasing RSBI in the acupuncture group. In subgroup analyses, the mean of RSBI significantly decreased 16.02 (with the SD in 60.84) in acupuncture group, while it increased 17.84 (with the SD in 39.38) in control group (p=0.036) after 12 sessions. Conclusion: Acupuncture treatment can improve breathing ability of patients with respirator dependence in respiratory care center.

Disrupting Transcription and Folate Biosynthesis Leads to Synergistic Suppression of Escherichia coli Growth.

The use of synergistic antibiotic combinations has emerged as a viable approach to contain the rapid spread of antibiotic-resistant pathogens. Here we report the discovery of a new strongly synergistic pair - microcin J25 and sulfamonomethoxine. The former is a lasso peptide that inhibits the function of RNA polymerase and the latter is a sulfonamide antibacterial agent that disrupts the folate pathway. Key to our discovery was a screening strategy that focuses on an antibiotic (microcin J25) that targets a hub (transcription) in the densely interconnected network of cellular pathways. The rationale was that disrupting such a hub likely weakens the entire network, generating weak links that potentiate the growth inhibitory effect of other antibiotics. We found that MccJ25 potentiates five other antibiotics as well. These results showcase the merit of taking a more targeted approach in the search and study of synergistic antibiotic pairs.

A case report of secondary synchronous diagnosis of multiple myeloma and systemic lupus erythematosus after breast cancer treatment: A CARE-compliant article.

INTRODUCTION: Breast cancer (BC) is the most diagnosed cancer worldwide. Multiple myeloma (MM) is a hematologic malignancy characterized by the overproduction of monoclonal antibodies in the bone marrow. Systemic lupus erythematosus (SLE) is distinguished by the aberrant activity of the immune system with heterogeneous clinical manifestations. The coexistence of more than one major illness in a patient can present a diagnostic challenge for clinical physicians, especially when the comorbid diseases share a similar clinical presentation. Herein, we report an unusual case of secondary synchronous diagnosis of MM and SLE after BC treatment. PATIENT CONCERNS: A 69-year-old female patient with breast cancer experienced severe skin itching and rashes on the face, anterior chest wall, back, and trunk for two days before admission. She had high levels of immunoglobulin and anti-nuclear antibodies; low levels of complements 3 and 4; positive anti-cardiolipin-IgM, anti-beta 2 glycoprotein-1 (anti-ß2GP1) antibodies, and lupus anticoagulant results at serological testing. DIAGNOSIS: The postoperative pathology report showed ductal carcinoma in situ in the right breast. SLE was confirmed based on the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria. IgG-κ type multiple myeloma was confirmed by bone marrow biopsy, and the patient was synchronously diagnosed with SLE and MM after BC treatment. INTERVENTIONS: Glucocorticoids and immunosuppressive agents, including intravenous hydrocortisone (5 g every 8 hours) and oral hydroxychloroquine (Plaquenil) (200 mg twice daily) were administered to treat SLE. One capsule of thalidomide 50 mg was administered orally every night at bedtime for MM. OUTCOMES: The patient died two days later, shortly after the administration of drugs, due to multiple organ failures secondary to pneumonia and respiratory failure. CONCLUSION: This is a case of MM and SLE after BC treatment. The present challenge was the early detection and accurate diagnosis of the secondary major illnesses, as the clinical manifestations were similar and non-specific between these two diseases. Awareness and prompt recognition of the common clinical symptoms of SLE and MM should be considered by clinical physicians to avoid delayed diagnoses and facilitate early treatment for a better prognosis.