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Resveratrol is a natural polyphenolic compound that shows great potential in neuroprotection, anti-inflammation,and antioxidation. Previous studies have demonstrated that resveratrol can effectively treat various animal models of retinal diseases. The aim of the research was to use an animal experimental model to assess the effectiveness of resveratrol in treating retinal-related diseases in various animal models of retinal diseases such as ischemia-reperfusion injury, diabetic retinopathy, glaucoma, chronic ocular hypertension, optic neuritis, age-related macular degeneration, and retinopathy of prematurity. Furthermore, this study aims to reveal the underlying mechanisms of resveratrol related to the treatment of retina-related diseases. A search was conducted across several databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and OVID. The search time was from the establishment of the database to October 2024 to collect studies on resveratrol intervention in animal models of retinal diseases. The studies included in this paper adopted the SYRCLE's risk of bias tool. Stata 16.0 and RevMan 5.4 software were used to analyze and visualize the results. Our meta-analysis comprises 26 studies and 365 animals demonstrates the following effects of resveratrol compared to the control group: a significant increase in the number of retinal ganglion cells (SMD = 3.91, 95% Cl = [2.97, 4.86], 0.00001) and superoxide dismutase activity (SMD = 3.14, 95% Cl = [0.96, 5.33], 0.005). Moreover, a decrease in malondialdehyde (SMD = -9.29,95% Cl = [-12.84, -5.74], 0.00001), reactive oxygen species level (SMD = -4.29,95% Cl = [-6.25, -2.32], 0.0001), cyclooxygenase-2 (SMD = -2.66, 95% Cl = [-4.01, -1.30], 0.0001), tumour necrosis factor-α(SMD = -3.96,95% Cl = [-6.27, -1.65], = 0.0008) and interleukin-6 (SMD = -3.32,95% Cl = [-4.20, -2.44], 0.00001) was observed. The A-wave amplitude and B-wave amplitude showed an increase respectively (MD = 105.92,95% Cl = [58.99, 152.84], 0.00001); (MD = 158.00,95% Cl = [86.35, 229.65], 0.0001), along with an increase in inner retinal thickness (SMD = 6.33, 95% CI = [5.10, 7.56], 0.00001) and total retinal thickness (SMD = 2.70, 95%Cl = [0.77, 4.83], 0.01). Subgroup analysis showed that different doses of resveratrol were associated with an increase in the number of RGCs ( 0.05). Resveratrol improves retinal diseases through multiple mechanisms: i) Neuroprotection: it activates the SIRT1/NF-κB and Nrf2 pathways, inhibits Caspase-3 expression, and promotes the survival of RGCs and ii) Antioxidation: it upregulates SOD activity, reduces the levels of MDA and ROS, and alleviates oxidative damage and iii) Anti-inflammation: it inhibits the COX-2, TNF-α, IL-6, and NF-κB pathways, alleviating the inflammatory response. These mechanisms resulted in enhanced amplitude of A/B waves, improved retinal thickness and visual function. Resveratrol has neuroprotective, anti-inflammatory and antioxidant effects through multiple mechanisms, thereby reducing retinal damage and maintaining the structure and function of the retina. This provides preclinical support for its possible therapeutic uses in the management of retinal diseases. https://www.crd.york.ac.uk/PROSPERO/myprospero.

To establish a Global Trigger Tool (GTT) method suitable for monitoring adverse drug events (ADEs) in the high-risk elderly inpatients with multiple chronic diseases, and to evaluate its sensitivity, specificity and feasibility. A total of 38 triggers were established by searching the literature and combining the characteristics of elderly hospitalized patients with multiple chronic diseases in Taizhou People's Hospital. A total of 480 elderly patients with multiple chronic diseases were sampled from January to December 2023, and the cases were reviewed. Adverse event grades were determined, and drug classes and organ-systems involved were analyzed; binary logistic regression and Receiver Operating Characteristic curves were adopted for analysis. Among the 480 cases, 123 cases were detected as having one or more positive triggers. ADEs occurred in 65 patients, with a total of 93 occurrences of ADEs; the highest number of ADE cases was observed in the administration of cardiovascular drugs, with 36 cases (38.71%). The highest organ-system involved in ADE was metabolic and nutritional disorders, with 47 cases (50.54%). The number of ADEs occurring in 1,000 patient-days was 22.90. The number of ADEs occurring in 100 patients was 19.38. Using binary logistic regression analysis, the risk factors were age and number of positive trigger detections for predicting the occurrence of ADEs. The GTT method had a sensitivity of 78.46%; specificity of 82.65%; compliance rate of 82.00%; Kappa value of 44.40%; and the Positive Predictive Value (PPV) was 41.46%. The GTT method has high sensitivity and specificity and is feasible; it has a relatively high PPV and is suitable for detecting ADEs in the high-risk elderly inpatients with multiple chronic diseases.

Nano-opto-electro-mechanical systems (NOEMS), considered as new platforms to study electronic and mechanical freedoms in the field of nanophotonics, have gained rapid progress in recent years. NOEMS offer exciting opportunities to manipulate information carriers using optical, electrical, and mechanical degrees of freedom, where the flow of light, dynamics of electrons, and mechanical vibration modes can be explored in both classical and quantum domains. By exploiting NOEMS concepts and technologies, high speed and low-power consumption switches, high-efficiency microwave-optical conversion devices, and multiple quantum information processing functions can be implemented through on-chip integration. This review will introduce the principles of NOEMS, summarize the recent developments, and important achievements, and give a prospect for the further applications and developments in this field.

Background This study explored the impact of MTM service on MMD patients with hypertension. Methods A total of 120 MMD inpatients from September to November 2019 were received and randomly divided into intervention group and control group. General services for noninfectious chronic diseases were given to the control group, while a standard MTM service was given to the intervention group. Patients’ blood pressure, EQ-5D utility value, readmission rate, drug-related problems, and average daily medication therapy cost were compared between the two groups and within the groups. This was done at the initial admission phase and in the first, third, sixth, and twelfth months after discharge. Results The intervention group had significantly lower blood pressure and average daily medication therapy cost 12 months after discharge compared to the control group (systolic blood pressure: P  = 0.023, diastolic blood pressure: P  < 0.001, average daily medication therapy cost: P  = 0.049); the number of DRPs decreased in both groups 12 months after discharge; the number of DRPs solved in the intervention group in the third, sixth and twelfth months after discharge were statistically higher compared with that in the control group ( P  = 0.013, P  = 0.012, P  = 0.001); there was no significant difference in the EQ-5D utility value and readmission rate between the two groups ( P  > 0.05). Conclusions MTM implementation in MMD patients can improve health outcomes and reduce healthcare-related costs among MMD patients. Trial registration Chinese Clinical Trial Register ChiCTR2200065111, date of registration: October 28, 2022.

Streptomyces lydicus has been reported to produce antibiotic streptolydigin. Pitching ratios play crucial roles in primary and secondary metabolism of Streptomyces bacteria. The higher pitching ratio (30%, v/v) significantly enhanced the levels of streptolydigin products in S. lydicus. Proteome analysis revealed that betaglucosidase and UTP-glucose-1-phosphate uridylyltransferase were up-regulated to accelerate the starch hydrolyzation at the high pitching ratios. Enhancement in the levels of UDP-N-acetylmuramoylalanyl-D-glutamate-2, 6-diaminopimelate ligase and glycine cleavage system aminomethyltransferase were involved in the conversion of amino acids into secondary metabolites. Additionally, the expression levels of PfkA2, PfkA3, Zwf2, SucD, GalE1, GatB, TktA1 and ThcA, associated with glycolysis, pentose phosphate pathway, TCA cycle and amino acid metabolism, were dramatically elevated at high pitching ratios, which play important roles in the enhanced streptolydigin production in S. lydicus E9. Interestingly, the levels of proteins (glutamine synthetase I, glutamate synthase subunit beta and glutamine synthetase) were down-regulated with the increases of pitching ratios and fermentation progress, revealing that pitching ratio altered the glutamine synthetase levels and consequently regulated the streptolydigin production of S. lydicus E9. The up-regulation of proteins (eg, aldehyde dehydrogenase and alkyl hydroperoxide reductase) was involved in the redox-based regulation network triggered by an imbalance of the intracellular cell redox homeostasis and by crosstalk with secondary metabolism at the higher pitching ratio. These results settle new insights into physiological facts of S. lydicus E9 in responses to pitching ratios and will eventually improve the antibiotic production schemes in industry.

Pitching ratio has been reported to impact not only on the primary metabolism, but also the secondary metabolism. Comparative metabolomics was used to explore the metabolic responses of Streptomyces lydicus E9 to pitching ratios (1, 10, and 30 %, v / v ). We identified more than 120 metabolites involved in glycolysis, tricarboxylic acid cycle, and amino acid and secondary metabolism, of which there are significant differences in the quantified 32 metabolites under different pitching ratios by gas chromatography coupled to time-of-flight mass spectrometry. The intracellular levels of most amino acids (e.g., valine, alanine, and isoleucine) declined with the increases of pitching ratios. Especially, the relative abundances of glutamate and proline were not only decreased with the increases of pitching rations, but also had much low level at stages II and III, which might be related to the significant enhancement in streptolydigin of S. lydicus E9 under 30 % high pitching ratio. Moreover, principal component analysis revealed that eight metabolites, including glucopyranoside, maltose, cAMP, glycine, proline, lysine, isoleucine, and valine, were considered as potential biomarkers to distinguish the influences of pitching ratios on streptolydigin production. Further investigations demonstrated that the additions of exogenous glutamate and proline (100 mg L −1 ) enhanced significantly the accumulation of streptolydigin, indicating that glutamate was the synthetic precursor of streptolydigin, while proline in S. lydicus E9 was converted into glutamate and consequently improved streptolydigin biosynthesis. Therefore, these findings provide new insights into the amino acid responses of S. lydicus E9 to pitching ratios and provide potential strategies to improve streptolydigin production.

This study explored the impact of MTM service on MMD patients with hypertension. A total of 120 MMD inpatients from September to November 2019 were received and randomly divided into intervention group and control group. General services for noninfectious chronic diseases were given to the control group, while a standard MTM service was given to the intervention group. Patients' blood pressure, EQ-5D utility value, readmission rate, drug-related problems, and average daily medication therapy cost were compared between the two groups and within the groups. This was done at the initial admission phase and in the first, third, sixth, and twelfth months after discharge. The intervention group had significantly lower blood pressure and average daily medication therapy cost 12 months after discharge compared to the control group (systolic blood pressure: P = 0.023, diastolic blood pressure: P < 0.001, average daily medication therapy cost: P = 0.049); the number of DRPs decreased in both groups 12 months after discharge; the number of DRPs solved in the intervention group in the third, sixth and twelfth months after discharge were statistically higher compared with that in the control group (P = 0.013, P = 0.012, P = 0.001); there was no significant difference in the EQ-5D utility value and readmission rate between the two groups (P > 0.05). MTM implementation in MMD patients can improve health outcomes and reduce healthcare-related costs among MMD patients.

The methyltransferase like 3 （METTL3）-containing methyltransferase complex catalyzes the N6-methyladenosine （m6A） formation, a novel epitranscriptomic marker; however, the nature of this complex remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms＇ tumor 1-associating protein （WTAP） and methyltransferase like 14 （METTL14）. WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic ac- tivity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-en- hanced crosslinking and immunoprecipitation （PAR-CLIP） illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism.

Objective： This study aimed to determine if gastric cardia adenocarcinoma （GCA） risk was associated with the lys （A or ＊2） allele at the rs671 （glu5041ys） polymorphism within the aldehyde dehydrogenase 2 （ALDH2） gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma （ESCC）. Methods： We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and low- incidence areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used to genotype the rs671 polymorphism. χ^2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA, and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups. Results： Compared with ALDH2＊1/＊1 homozygotes, ALDH2＊1/＊2 and ALDH2＊2/＊2 carriers did not increase the risk for GCA in the Chinese Han population （P〉0.05）. Interestingly, the ratio of homozygous or heterozygous ALDH2 ＊2 carriers in high- incidence areas for both GCA and ESCC was lower than that in low-incidence areas （P〈0.001）. Conclusions： Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Evolutionarily conserved DDB1‐and CUL4‐associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING‐finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome‐wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co‐immunoprecipitation assays revealed that DCAF13 and DNA damage‐binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets. DCAF13 is overexpressed in breast cancer and its overexpression closely correlates with the poor prognosis. DCAF13 deletion markedly decreased breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo.DCAF13 promotes breast cancer cell proliferation by inhibiting the expression of PERP.