Semi-rational design of nitroarene dioxygenase for catalytic ability toward 2,4-dichloronitrobenzene.

Rieske non-heme dioxygenase family enzymes play an important role in the aerobic biodegradation of nitroaromatic pollutants, but no active dioxygenases are available in nature for initial reactions in the degradation of many refractory pollutants like 2,4-dichloronitrobenzene (24DCNB). Here, we report the engineering of hotspots in 2,3-dichloronitrobenzene dioxygenase from Diaphorobacter sp. strain JS3051, achieved through molecular dynamic simulation analysis and site-directed mutagenesis, with the aim of enhancing its catalytic activity toward 24DCNB. The computationally predicted activity scores were largely consistent with the detected activities in wet experiments. Among them, the two most beneficial mutations (E204M and M248I) were obtained, and the combined mutant reached up to a 62-fold increase in activity toward 24DCNB, generating a single product, 3,5-dichlorocatechol, which is a naturally occurring compound. In silico analysis confirmed that residue 204 affected the substrate preference for meta-substituted nitroarenes, while residue 248 may influence substrate preference by interaction with residue 295. Overall, this study provides a framework for manipulating nitroarene dioxygenases using computational methods to address various nitroarene contamination problems.IMPORTANCEAs a result of human activities, various nitroaromatic pollutants continue to enter the biosphere with poor degradability, and dioxygenation is an important kickoff step to remove toxic nitro-groups and convert them into degradable products. The biodegradation of many nitroarenes has been reported over the decades; however, many others still lack corresponding enzymes to initiate their degradation. Although rieske non-heme dioxygenase family enzymes play extraordinarily important roles in the aerobic biodegradation of various nitroaromatic pollutants, prediction of their substrate specificity is difficult. This work greatly improved the catalytic activity of dioxygenase against 2,4-dichloronitrobenzene by computer-aided semi-rational design, paving a new way for the evolution strategy of nitroarene dioxygenase. This study highlights the potential for using enzyme structure-function information with computational pre-screening methods to rapidly tailor the catalytic functions of enzymes toward poorly biodegradable contaminants.

Epoxy Resins with Controllable "Thermally Conductive-Self-Healing" Synergies: a New Material to Meet the Needs of Flexible Electronic Devices.

With the popularization of 5G technology and artificial intelligence, thermally conductive epoxies with self-healing ability will be widely used in flexible electronic materials. Although many compounds containing both performances have been synthesized, there is little systematic theory to explain this coordination mechanism. In this paper, alkyl chains of different lengths were introduced to epoxies for discussing the thermally conductive, the self-healing performance, and the synergistic effect. A series of electronic-grade biphenyl epoxies (4,4'-bis(oxiran-2-ylmethoxy)-1,1'-biphenyl (1), 4,4'-bis(2-(oxiran-2-yl)ethoxy)-1,1'-biphenyl (2), 4,4'-bis(3-(oxiran-2-yl)propoxy)-1,1'-biphenyl (3), and 4,4'-bis(4-(oxiran-2-yl)butoxy)-1,1'-biphenyl (4) were synthesized and characterized. Furthermore, they were cured with decanedioic acid to produce polymers. Results showed that alkyl chains can both affect the two properties, and the epoxies suitable for specific application scenarios can be prepared by adjusting the length of alkyl chains. In terms of thermal conductivity, compound 1 was a most promising material. However, compound 4 was expected to be utilized in flexible electronic devices because of its acceptable thermal conductivity, self-healing ability, transparency, and flexibility.

Tra2ß exerts tumor-promoting effects via GSK3/ß-catenin signaling in oral squamous cell carcinoma.

OBJECTIVES: The splicing factor transformer-2 homolog beta (Tra2ß) plays a pivotal role in various cancers. Nonetheless, its role in oral squamous cell carcinoma (OSCC) has not been comprehensively explored. This study sought to discern the influence of Tra2ß on OSCC and its underlying mechanisms. MATERIALS AND METHODS: We assessed Tra2ß expression in OSCC utilizing immunohistochemistry, qRT-PCR, and western blotting techniques. siRNA transfection was used to silence Tra2ß. Whole transcriptome RNA sequencing (RNA-seq) analysis was carried out to reveal the alternative splicing (AS) events. KEGG pathway analysis enriched the related pathways. Colony formation, transwell, wound healing, and Annexin V-FITC/PI were employed to appraise the consequences of Tra2ß silencing on OSCC. RESULTS: Tra2ß was highly expressed in both OSCC tissues and cell lines. Knockdown of Tra2ß-regulated AS events with skipped exon (SE) accounts for the highest proportion. Meanwhile, downregulation of Tra2ß reduced cell proliferation, migration, and invasion, however increasing cell apoptosis. Moreover, Wnt signaling pathway involved in the function of Tra2ß knockdown which was demonstrated directly by a discernible reduction in the expression of GSK3/ß-catenin signaling axis. CONCLUSIONS: These findings suggest that knockdown of Tra2ß may exert anti-tumor effects through the GSK3/ß-catenin signaling pathway in OSCC.

Combined effects of azoxystrobin and oxytetracycline on rhizosphere microbiota of Arabidopsis thaliana.

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

A Novel IRAK4 Inhibitor DW18134 Ameliorates Peritonitis and Inflammatory Bowel Disease.

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.

The Differences in the Developmental Stages of the Cardiomyocytes and Endothelial Cells in Human and Mouse Embryos at the Single-Cell Level.

Our research focuses on expression patterns in human and mouse embryonic cardiomyocytes and endothelial cells at the single-cell level. We analyzed single-cell datasets containing different species, cardiac chambers, and cell types. We identified developmentally dynamic genes associated with different cellular lineages in the heart and explored their expression and possible roles during cardiac development. We used dynamic time warping, a method that aligns temporal sequences, to compare these developmental stages across two species. Our results indicated that atrial cardiomyocytes from E9.5 to E13.5 in mice corresponded to a human embryo age of approximately 5-6 weeks, whereas in ventricular cardiomyocytes, they corresponded to a human embryo age of 13-15 weeks. The endothelial cells in mouse hearts corresponded to 6-7-week-old human embryos. Next, we focused on expression changes in cardiac transcription factors over time in different species and chambers, and found that Prdm16 might be related to interspecies cardiomyocyte differences. Moreover, we compared the developmental trajectories of cardiomyocytes differentiated from human pluripotent stem cells and embryonic cells. This analysis explored the relationship between their respective developments and provided compelling evidence supporting the relevance of our dynamic time-warping results. These significant findings contribute to a deeper understanding of cardiac development across different species.

Superselective Arterial Hyaluronidase Thrombolysis is an Effective Treatment for Hyaluronic Acid-Induced Retinal Artery Occlusion: Study in a Rabbit Model.

BACKGROUND: There are serious complications associated with hyaluronic acid (HA) facial injections, including vision impairment due to retinal artery ischemia. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in rabbit. We used this to verify the efficacy of hyaluronidase intra-artery thrombolysis in the treatment of hyaluronic acid-induced retinal artery occlusion. METHODS: Retinal artery ischemia was induced by injecting HA into the ophthalmic artery (OA) of adult chinchilla rabbit, and reperfusion was achieved by intra-artery thrombolysis therapy with hyaluronidase following 60 min and 4 h of occlusion. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow in the retina. Electroretinogram (ERG), hematoxylin and eosin staining and transmission electron microscope were used to evaluate the structure and function of the retina after ischemia and reperfusion following 60 min and 4 h of occlusion. RESULTS: DSA and FFA images confirmed occlusion of the ophthalmic and central retinal arteries, as well as reperfusion after hyaluronidase thrombolysis. ERG indicated retinal dysfunction following ischemia, and thrombolysis partially rescued its impairment following 4 h of occlusion. Hematoxylin and eosin staining and TUNEL staining revealed ischemia-induced histological damages in the retina at different time windows, and hyaluronidase thrombolysis partially mitigated these damages. CONCLUSIONS: We report a method to establish a HA-induced retinal artery occlusion animal model. Hyaluronidase intra-artery thrombolysis was used to recanalize the embolized OA at different time points. Using our method, we achieved retinal reperfusion, and an improvement was observed in the visual function of rabbits after hyaluronidase thrombolysis following 4 h of occlusion. We believe that hyaluronidase intra-artery thrombolysis is an effective method to treat HA-induced retinal artery occlusion in clinic. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The unique salt bridge network in GlacPETase: a key to its stability.

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.

Contribution of Matrix Metalloproteinase-2 Genotypes to Taiwan Pterygium Risk.

BACKGROUND/AIM: In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk. MATERIALS AND METHODS: MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology. RESULTS: The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136). CONCLUSION: The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese.

Characteristics of patients with chronic hepatitis B infection in China: A retrospective claims database study.

Chronic hepatitis B (CHB) infection affects approximately 90 million people in China, where there are profoundly unmet clinical and public health needs. This study evaluated patient demographics, disease progression, and treatment management using national administrative claims data. This retrospective, observational study used anonymized data from the China Health Insurance Research Association claims database (January 1-December 31, 2016); data that could not be validated, or from duplicate entries, were excluded. Patients were identified using the International Classification of Diseases, 10th Revision diagnostic code for CHB (B18.0 and B18.1), using keyword searches for "CHB or HBV" and free-text descriptions of CHB treatments including nucleos(t)ide analogues. Primary objectives included evaluation of: demographics and clinical characteristics of patients with CHB, overall and by presence or absence of cirrhosis and hospital tier; proportion of patients prescribed CHB treatment; and healthcare costs and utilization overall and by presence or absence of cirrhosis and hospital tier. Most identified patients with CHB were male, aged 25 to 65 years, resided in East China, and had employee health insurance. Cirrhosis was common (16.20%) and associated with male preponderance, older age, hepatitis C virus coinfection, and higher hospital care demands and costs. The most frequently visited hospitals were Tier III; patients visiting Tier III generally required more hospital care compared with those visiting Tier I/II hospitals. Only two-thirds of patients were prescribed antiviral therapy for CHB (most commonly nucleos(t)ide analogues). Results from this study highlight a substantial need to improve access to appropriate CHB treatment in China.

The optimal blood glucose is significantly associated with lower mortality in critically ill patients with cardiogenic shock: an analysis revealed with time series blood glucose records.

BACKGROUND: The optimal blood glucose (BG) level for patients with cardiogenic shock in the intensive care unit (ICU) remains unclear. Studies have found that both excessively high and low BG levels contribute to adverse cardiovascular events. Our study aims to investigate the optimal BG level for critically ill patients with cardiogenic shock and evaluate the effects of optimal BG on the prognosis of patients. METHODS: A total of 2013 patients with cardiogenic shock obtained from the Medical Information Mart for Intensive Care (MIMIC) IV database were included in the final cohort for our retrospective observational study for data analysis. The exposure was time-weighted average BG (TWA-BG), which was calculated by the time-series BG records and corresponding time stamps of patients with cardiogenic shock during their stay in the ICU. The cut-off value of TWA-BG was identified by the restricted cubic spline curve and included patients were categorized into three groups: low TWA-BG group (TWA-BG ≤ 104 mg/dl), optimal TWA-BG group (104 < TWA-BG ≤ 138 mg/dl), and high TWA-BG group (TWA-BG > 138 mg/dl). The primary outcome was 28-day mortality, and the secondary outcomes were ICU and in-hospital mortality. We performed the log-rank test to detect whether there is a difference in mortality among different groups in the original cohort. Multiple distinct models were employed to validate the robustness of the results. RESULTS: Our study revealed that the optimal BG level for critically ill patients with cardiogenic shock is 104-138 mg/dl. Compared to the optimal TWA-BG group, the low TWA-BG group (hazard ratio (HR): 1.67, 95% confidence interval (CI): 1.19-2.33, p = 0.002) and high TWA-BG group (HR: 1.72, 95% CI: 1.46-2.03, p < 0.001) exhibited higher 28-day mortality. Similarly, the low TWA-BG group and high TWA-BG group demonstrated higher risks in terms of ICU mortality (low TWA-BG group: HR: 2.30, 95% CI: 1.40-3.79, p < 0.001; high TWA-BG group: HR: 1.77, 95% CI: 1.45-2.17, p < 0.001) and in-hospital mortality (low TWA-BG group: HR: 1.73, 95% CI: 1.19-2.51, p = 0.001; high TWA-BG group: HR: 1.64, 95% CI: 1.38-1.95, p < 0.001). Sensitivity analysis conducted through propensity score matching and the subgroup analysis further substantiated the robustness of the results. CONCLUSION: The optimal BG level for patients with cardiogenic shock is 104-138 mg/dl. BG levels below 104 mg/dl and above 138 mg/dl were associated with a less favorable prognosis.

Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis.

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.

AlmA involved in the long-chain n-alkane degradation pathway in Acinetobacter baylyi ADP1 is a Baeyer-Villiger monooxygenase.

Many Acinetobacter species can grow on n-alkanes of varying lengths (≤C40). AlmA, a unique flavoprotein in these Acinetobacter strains, is the only enzyme proven to be required for the degradation of long-chain (LC) n-alkanes, including C32 and C36 alkanes. Although it is commonly presumed to be a terminal hydroxylase, its role in n-alkane degradation remains elusive. In this study, we conducted physiological, biochemical, and bioinformatics analyses of AlmA to determine its role in n-alkane degradation by Acinetobacter baylyi ADP1. Consistent with previous reports, gene deletion analysis showed that almA was vital for the degradation of LC n-alkanes (C26-C36). Additionally, enzymatic analysis revealed that AlmA catalyzed the conversion of aliphatic 2-ketones (C10-C16) to their corresponding esters, but it did not conduct n-alkane hydroxylation under the same conditions, thus suggesting that AlmA in strain ADP1 possesses Baeyer-Villiger monooxygenase (BVMO) activity. These results were further confirmed by bioinformatics analysis, which revealed that AlmA was closer to functionally identified BVMOs than to hydroxylases. Altogether, the results of our study suggest that LC n-alkane degradation by strain ADP1 possibly follows a novel subterminal oxidation pathway that is distinct from the terminal oxidation pathway followed for short-chain n-alkane degradation. Furthermore, our findings suggest that AlmA catalyzes the third reaction in the LC n-alkane degradation pathway.IMPORTANCEMany microbial studies on n-alkane degradation are focused on the genes involved in short-chain n-alkane (≤C16) degradation; however, reports on the genes involved in long-chain (LC) n-alkane (>C20) degradation are limited. Thus far, only AlmA has been reported to be involved in LC n-alkane degradation by Acinetobacter spp.; however, its role in the n-alkane degradation pathway remains elusive. In this study, we conducted a detailed characterization of AlmA in A. baylyi ADP1 and found that AlmA exhibits Baeyer-Villiger monooxygenase activity, thus indicating the presence of a novel LC n-alkane biodegradation mechanism in strain ADP1.

Epstein-Barr Virus Uveitis Confirmed via Aqueous Humor Polymerase Chain Reaction and Metagenomics-A Case Report.

This is a case report of Epstein-Barr virus (EBV) uveitis confirmed via aqueous humor polymerase chain reaction (PCR) and metagenomics. This 72-year-old male with a history of diabetes and herpes zoster complained of redness and blurred vision in his right eye for eight months. Mild conjunctival injection, anterior chamber cells, mutton-fat keratic precipitates, and vitreous haze were noted. Fluorescein angiography revealed dye leakage from retinal vessels without retinal ischemic changes. Only the serum anti-cytomegalovirus (CMV) IgG was positive while the aqueous humor PCR for VZV (Varicella-zoster virus), HSV (Herpes simplex viruses), CMV, and EBV was initially negative. Inflammation recurred and vitreous haze worsened after discontinuing nine-month topical ganciclovir and oral prednisolone. the aqueous humor PCR was repeated due to persistent low-grade inflammation. The EBV PCR turned out to be positive. Shotgun metagenomics revealed 1459 classified sequences (1.62%) and confirmed the EBV infection. Topical ganciclovir and methylprednisolone treatment was resumed. Conjunctival injection improved while pigmented keratic precipitates lessened. Elderly patients with diabetes or under immunosuppression may be susceptible to chronic uveitis associated with subsequent EBV infection. Repeated aqueous humor PCR and shotgun metagenomics are important tools in the diagnosis of this case of chronic indolent panuveitis.

Prevalence of uveitis in syphilis patients in Taiwan.

Few population-based studies have looked at the risk of uveitis among syphilis patients. Our study addresses the knowledge gap by reporting on uveitis risk in syphilis patients through a retrospective cohort study. The Taiwan National Health Insurance database was used for this study, covering the period from January 1st, 2009, to December 31st, 2020. We created a 1:4 propensity score matched cohort between the syphilis patients and controls, which accounted for gender, age, and comorbidities. The primary endpoint was the incidence of newly recorded uveitis. The assessment of uveitis risk in syphilis patients included the use of the Kaplan-Meier method and multivariate Cox proportional hazard model. A total of 31,597 syphilis patients and 126,379 matched comparisons were recruited. The uveitis incidence rate from our syphilis patients was 1.25 per 1000 person-years. The uveitis incidence rate from our non-syphilis group was 0.8 per 1000 person-years. After matching, the syphilis group was found to have a higher risk of developing uveitis (adjusted hazard ratio (aHR) [95% CI]: 1.57 [1.36-1.81], P < .001). Among males and individuals aged 20-34 years, subgroup analysis showed an increased risk of uveitis in the presence of syphilis infection. The Kaplan-Meier survival curve showed a significant difference in uveitis incidence between syphilis and non-syphilis groups (log-rank test P < .001). In summary, our study revealed that Taiwanese syphilis patients were at a higher risk of developing uveitis. These results highlight the need for regular ocular monitoring and screening in individuals with syphilis.

The Significant Contribution of Interleukin-16 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection to Gastric Cancer.

BACKGROUND/AIM: Elevated serum interleukin-16 (IL-16) levels have been reported in gastric cancer (GC) tissues; however, the role of IL-16 genotypes in GC susceptibility remains largely unexplored. This study aimed to investigate the contribution of IL-16 genotypes to GC susceptibility and to assess their interactions with smoking, alcohol drinking, and Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology was employed to determine IL-16 rs4778889, rs11556218, and rs4072111 genotypic characteristics in 161 patients with GC and 483 controls. RESULTS: Significant differences were observed in the distribution of genotypic (p=0.0009) and allelic (p=0.0002) frequencies of IL-16 rs11556218 among cases and controls. Specifically, the frequencies of TG and GG genotypes of IL-16 rs11556218 were 37.3% and 6.8% among patients with GC, respectively, which were higher than those among the controls (26.7% and 2.7%). In contrast, no significant differences were found concerning IL-16 rs4778889 or rs4072111. Notably, individuals with IL-16 rs11556218 TT genotypes exhibited significant protective effects against GC when exposed to risk factors, such as smoking, alcohol drinking, and H. pylori infection. CONCLUSION: IL-16 rs11556218 T allele was associated with reduced susceptibility to GC. Furthermore, carriers of the TT genotype showed protection against GC risk factors, including smoking, alcohol drinking, and H. pylori infection. These findings provide valuable insights into the potential role of IL-16 genotypes in GC development and their interactions with lifestyle and infectious factors.

Cytogenetics and molecular genetics of myelodysplastic neoplasms.

According to the 2022 World Health Organization (WHO) Classification (5th edition), the term myelodysplastic neoplasms (abbreviated MDS) has been introduced to replace myelodysplastic syndromes. MDS are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more of lineages, ineffective hematopoiesis, and an increased risk of progression to bone marrow failure or to acute myeloid leukemia (AML). Current NCCN guidelines and recent review articles have provided in depth discussion on the clinical diagnosis and management of MDS. This review will focus on discussion of the WHO and International Consensus Classification (ICC) updates on the role of cytogenetics and molecular genetics in the diagnosis and risk stratification of MDS.

[Application of lingual wedge shaped coronectomy in extraction of horizontally impacted mandibular third molars].

PURPOSE: To investigate the effect of lingual wedge shaped coronectomy in extraction of horizontally impacted mandibular third molar(HIMTM). METHODS: A total of 172 patients with HIMTM were randomly divided into experimental group and routine group with 86 cases in each group . Lingual wedge-shaped coronectomy was applied in the experimental group and T-shaped coronectomy was applied in routine group. Operation time, intraoperative and postoperative complications were compared between the two groups.The data were analyzed by using SPSS 26.0 software package. RESULTS: The operation time of the experimental group was significantly shorter than that of the control group (P＜0.05). The rate of swelling, pain, lingual bone plate injury and broken root of the experimental group were separately lower than that of the control group, and the difference was statistically significant(P＜0.05). CONCLUSIONS: Lingual wedge shaped coronectomy of HIMTM has significant advantages in the extraction of HIMTM. It can reduce operation time，broken roots,fracture of lingual plate, postoperative swelling, pain and other surgical complications.