[Study on methods measuring mechanical properties of arterial wall by macroscopic indentation].

Accurately evaluating the local biomechanics of arterial wall is crucial for diagnosing and treating arterial diseases. Indentation measurement can be used to evaluate the local mechanical properties of the artery. However, the effects of the indenter's geometric structure and the analysis theory on measurement results remain uncertain. In this paper, four kinds of indenters were used to measure the pulmonary aorta, the proximal thoracic aorta and the distal thoracic aorta in pigs, and the arterial elastic modulus was calculated by Sneddon and Sirghi theory to explore the influence of the indenter geometry and analysis theory on the measured elastic modulus. The results showed that the arterial elastic modulus measured by cylindrical indenter was lower than that measured by spherical indenter. In addition, compared with the calculated results of Sirghi theory, the Sneddon theory, which does not take adhesion forces in account, resulted in slightly larger elastic modulus values. In conclusion, this study provides parametric support for effective measurement of arterial local mechanical properties by millimeter indentation technique.

Fabrication and performance evaluation of a design for an extended depth-of-focus intraocular lens based on an improved sinusoidal profile.

This study presents the fabrication and evaluation of a sinusoidal extended depth-of-focus (EDoF) intraocular lens (IOL) based on our previously proposed design approach. The power, through-focus MTF, and surface profile were measured using commercial instruments. Through-focus images of a United States Air Force (USAF) 1951 resolution target formed by the fabricated IOL were compared with Symfony and AR40E under monochromatic and polychromatic light using optical bench testing. Simulations assessed visual acuity (VA) of a pseudophakic model eye with the EDoF IOL, including evaluation of tilt and decentration effects. Results indicate that the base power, add power, and the through-focus MTF@50 lp/mm of the fabricated IOL at a 3 mm pupil size align with the design specifications. The extended-depth-of-focus and imaging performance for the far vision of the fabricated IOL under both monochromatic and polychromatic light conditions at a 3.0 mm pupil diameter is comparable to that of Symfony. In addition, the fabricated IOL exhibits a similar extended-depth-of-focus for three discrete wavelengths. The pseudophakic model eye with the designed EDoF IOL demonstrates a VA exceeding 0.1 logMAR within a defocus range of 2.44 D. The VA is tolerant to both IOL tilt and decentration. These findings demonstrate the promising potential of the sinusoidal EDoF IOL design for future applications in cataract surgery.

A prominent role of LncRNA H19 in H. pylori CagA induced DNA damage response and cell malignancy.

Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Urinary α 1-microglobulin and ß 2-microglobulin as markers of early kidney injury in HIV-positive male patients on tenofovir-based antiretroviral therapy.

BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.

WRKY transcription factors modulate flowering time in four Arachis species: a bioinformatics analysis.

BACKGROUND: WRKY proteins are important transcription factors (TFs) in plants, involved in growth and development and responses to environmental changes. Although WRKY TFs have been studied at the genome level in Arachis genus, including oil crop and turfgrass, their regulatory networks in controlling flowering time remain unclear. The aim of this study was to predict the molecular mechanisms of WRKY TFs regulation flowering time in Arachis genus at the genome level using bioinformatics approaches. RESULTS: The flowering-time genes of Arachis genus were retrieved from the flowering-time gene database. The regulatory networks between WRKY TFs and downstream genes in Arachis genus were predicted using bioinformatics tools. The results showed that WRKY TFs were involved in aging, autonomous, circadian clock, hormone, photoperiod, sugar, temperature, and vernalization pathways to modulate flowering time in Arachis duranensis, Arachis ipaensis, Arachis monticola, and Arachis hypogaea cv. Tifrunner. The WRKY TF binding sites in homologous flowering-time genes exhibited asymmetric evolutionary pattern, indicating that the WRKY TFs interact with other transcription factors to modulate flowering time in the four Arachis species. Protein interaction network analysis showed that WRKY TFs interacted with FRUITFULL and APETALA2 to modulate flowering time in the four Arachis species. WRKY TFs implicated in regulating flowering time had low expression levels, whereas their interaction proteins had varying expression patterns in 22 tissues of A. hypogaea cv. Tifrunner. These results indicate that WRKY TFs exhibit antagonistic or synergistic interactions with the associated proteins. CONCLUSIONS: This study reveals complex regulatory networks through which WRKY TFs modulate flowering time in the four Arachis species using bioinformatics approaches.

Altered temporal lobe connectivity is associated with psychotic symptoms in drug-naïve adolescent patients with first-episode schizophrenia.

Research on individuals with a younger onset age of schizophrenia is important for identifying neurobiological processes derived from the interaction of genes and the environment that lead to the manifestation of schizophrenia. Schizophrenia has long been recognized as a disorder of dysconnectivity, but it is largely unknown how brain connectivity changes are associated with psychotic symptoms. Twenty-one adolescent-onset schizophrenia (AOS) patients and 21 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) was used to investigate local brain connectivity alterations in AOS. Regions with significant ReHo changes in patients were selected as "seeds" for further functional connectivity (FC) analysis and Granger causality analysis (GCA), and associations of the obtained functional brain measures with psychotic symptoms in patients with AOS were examined. Compared with HCs, AOS patients showed significantly increased ReHo in the right middle temporal gyrus (MTG), which was positively correlated with PANSS-positive scores, PSYRATS-delusion scores and auditory hallucination scores. With the MTG as the seed, lower connectivity with the bilateral postcentral gyrus (PCG) and higher connectivity with the right precuneus were observed in patients. The reduced FC between the right MTG and bilateral PCG was significantly and positively correlated with hallucination scores. GCA indicated decreased Granger causality from the right MTG to the left middle frontal gyrus (MFG) and from the right MFG to the right MTG in AOS patients, but such effects did not significantly associate with psychotic symptoms. Abnormalities in the connectivity within the MTG and its connectivity with other networks were identified and were significantly correlated with hallucination and delusion ratings. This region may be a key neural substrate of psychotic symptoms in AOS.

TIPE1 limits virus replication by disrupting PKM2/ HIF-1α/ glycolysis feedback loop.

OBJECTIVE: Virus infection is a major threat to human health and remains a significant cause of death to date. Macrophages are important innate immune cells that exhibit indispensable roles in controlling virus replication. It was recently reported that metabolic adaption determines the functional state of macrophages. Thus, to further unravel the crucial factors involving in metabolic adaption of macrophages might provide the potential candidates for optimizing their anti-viral capabilities. METHODS: RT-PCR, Western blotting, virus plaque assay and HE were used to evaluate the viral load in virus-infected Tipe1M-KO and Tipe1f/f mice or cultured macrophages. RNA sequencing were performed with Tipe1M-KOor Tipe1f/f BMDMs upon virus infection. Extracellular acidification rate (ECAR) was applied for analyzing glycolysis rate in virus-infected BMDMs. Co-immunoprecipitation (Co-IP) assay and LC-MS/MS were used to determine the potential interacting proteins of TIPE1. RESULTS: TIPE1 level was significantly reduced in BMDMs infected with either RNA viruses or DNA virus. Deficiency of Tipe1 in macrophages increased viral load and aggravated tissue damage. Mechanistically, TIPE1 suppressed the glycolytic capacity of macrophages through interacting with PKM2 and promoting its ubiquitination degradation, which in turn decreased HIF1α transcription and viral replication in macrophages. CONCLUSIONS: TIPE1 functions as a novel regulator for metabolic reprogramming and virus infection in macrophages.

Differences between psoriatic arthritis and psoriasis in multi-omics.

We aim to systemically review the genomics, transcriptomics, epigenetics, proteomics, metabonomics and microbiota of psoriatic arthritis and psoriasis, illustrating the differences of these two diseases, broadening our understanding of the pathogenesis of them and providing important clues for valuable biomarkers of earlier diagnosis and treatments. To our knowledge, this is the first study that combine all omics studies from genomics to microbiota and may serve as a reference for future studies to identify the key underlying pathways in psoriatic arthritis.

Investigation of the causal association between Parkinson's disease and autoimmune disorders: a bidirectional Mendelian randomization study.

Background: To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk. Methods: By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results. Results: Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility. Conclusion: In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.

BJLD-CMI: a predictive circRNA-miRNA interactions model combining multi-angle feature information.

Increasing research findings suggest that circular RNA (circRNA) exerts a crucial function in the pathogenesis of complex human diseases by binding to miRNA. Identifying their potential interactions is of paramount importance for the diagnosis and treatment of diseases. However, long cycles, small scales, and time-consuming processes characterize previous biological wet experiments. Consequently, the use of an efficient computational model to forecast the interactions between circRNA and miRNA is gradually becoming mainstream. In this study, we present a new prediction model named BJLD-CMI. The model extracts circRNA sequence features and miRNA sequence features by applying Jaccard and Bert's method and organically integrates them to obtain CMI attribute features, and then uses the graph embedding method Line to extract CMI behavioral features based on the known circRNA-miRNA correlation graph information. And then we predict the potential circRNA-miRNA interactions by fusing the multi-angle feature information such as attribute and behavior through Autoencoder in Autoencoder Networks. BJLD-CMI attained 94.95% and 90.69% of the area under the ROC curve on the CMI-9589 and CMI-9905 datasets. When compared with existing models, the results indicate that BJLD-CMI exhibits the best overall competence. During the case study experiment, we conducted a PubMed literature search to confirm that out of the top 10 predicted CMIs, seven pairs did indeed exist. These results suggest that BJLD-CMI is an effective method for predicting interactions between circRNAs and miRNAs. It provides a valuable candidate for biological wet experiments and can reduce the burden of researchers.

First total synthesis, antitumor evaluation and target identification of mornaphthoate E: A new tubulin inhibitor template acting on PI3K/Akt signaling pathway.

Mornaphthoate E (MPE) is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines. In the current project, the first total synthesis of (±)-MPE was achieved in seven steps and 5.6% overall yield. Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells, with the levoisomer exerting slightly better potency. The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model. Notably, MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage. Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling. In conclusion, our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

The Fabrication of a Customized Surgical Template for a Miniscrew Placement Using a Fully Digitized Process.

This report presents a clinical case involving the application of a computer-aided design and manufacturing (CAD-CAM) guide to insert miniscrew anchorage at the zygomatic alveolar ridge. A 24-year-old male adult came in with overcrowded teeth and a protruding facial profile, particularly severe overcrowding in the upper teeth and moderate overcrowding in the lower teeth. The orthodontic treatment plan involved extracting four first premolars and adding a mini-implant in the upper jaw to enhance anchorage. A miniscrew was placed in the patient's left zygomatic alveolar ridge using a guide and in the right zygomatic alveolar ridge based on experience. The use of a mini-implant guide improves the accuracy of mini-implant positioning and angulation in the infrazygomatic crest zone, reduces the risk of tooth root damage, and enhances mini-implant stability.

A Carbon 21 Steroidal Glycoside with Pregnane Skeleton from Cynanchum atratum Bunge Promotes Megakaryocytic and Erythroid Differentiation in Erythroleukemia HEL Cells through Regulating Platelet-Derived Growth Factor Receptor Beta and JAK2/STAT3 Pathway.

Erythroleukemia is a rare form of acute myeloid leukemia (AML). Its molecular pathogenesis remains vague, and this disease has no specific therapeutic treatments. Previously, our group isolated a series of Carbon 21 (C-21) steroidal glycosides with pregnane skeleton from the root of Cynanchum atratum Bunge. Among them, we found that a compound, named BW18, can induce S-phase cell cycle arrest and apoptosis via the mitogen-activated protein kinase (MAPK) pathway in human chronic myeloid leukemia K562 cells. However, its anti-tumor activity against erythroleukemia remains largely unknown. In this study, we aimed to investigate the anti-erythroleukemia activity of BW18 and the underlying molecular mechanisms. Our results demonstrated that BW18 exhibited a good anti-erythroleukemia activity in the human erythroleukemia cell line HEL and an in vivo xenograft mouse model. In addition, BW18 induced cell cycle arrest at the G2/M phase and promoted megakaryocytic and erythroid differentiation in HEL cells. Furthermore, RNA sequencing (RNA-seq) and rescue assay demonstrated that overexpression of platelet-derived growth factor receptor beta (PDGFRB) reversed BW18-induced megakaryocytic differentiation in HEL cells, but not erythroid differentiation. In addition, the network pharmacology analysis, the molecular docking and cellular thermal shift assay (CETSA) revealed that BW18 could inactivate Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, which might mediate BW18-induced erythroid differentiation. Taken together, our findings elucidated a novel role of PDGFRB in regulating erythroleukemia differentiation and highlighted BW18 as an attractive lead compound for erythroleukemia treatment.

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis.

Purpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71. Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot. Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts. Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.

ZAP facilitates NLRP3 inflammasome activation via promoting the oligomerization of NLRP3.

The NOD-like receptor family protein 3 (NLRP3) inflammasome is a crucial complex for the host to establish inflammatory immune responses and plays vital roles in a series of disorders, including Alzheimer's disease and acute peritonitis. However, its regulatory mechanism remains largely unclear. Zinc finger antiviral protein (ZAP), also known as zinc finger CCCH-type antiviral protein 1 (ZC3HAV1), promotes viral RNA degradation and plays vital roles in host antiviral immune responses. However, the role of ZAP in inflammation, especially in NLRP3 activation, is unclear. Here, we show that ZAP interacts with NLRP3 and promotes NLRP3 oligomerization, thus facilitating NLRP3 inflammasome activation in peritoneal macrophages of C57BL/6 mice. The shorter isoform of ZAP (ZAPS) appears to play a greater role than the full-length isoform (ZAPL) in HEK293T cells. Congruously, Zap-deficient C57BL/6 mice may be less susceptible to alum-induced peritonitis and lipopolysaccharide-induced sepsis in vivo. Therefore, we propose that ZAP is a positive regulator of NLRP3 activation and a potential therapeutic target for NLRP3-related inflammatory disorders.

The anti-colorectal cancer effect and metabolites of Agrimonia pilosa Ledeb.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of γδT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.

Endoscopic Balloon Dilatation of the Eustachian Tube via the Soft Palate Approach in Miniature Pigs.

The eustachian tube (ET) is one of the most complex organs in the human body, and its dysfunction may lead to a variety of diseases. In recent years, an increasing number of scholars have opted to conduct ET-related studies using large experimental animals such as miniature pigs or sheep, yielding promising results. Typically, conventional endoscopic procedures are performed through the nasal approach for large experimental animals. However, due to the elongated and narrow nasal cavity in these animals, transnasal surgeries are challenging. To address this issue, we explored an ET surgery approach via the soft palate. The animal was placed in a supine position. After endotracheal intubation under general anesthesia, a mouth opener was used to fully expose the upper palate. Local infiltration with diluted adrenal fluid was performed for anesthesia of the area. A sickle knife was then used to make a longitudinal soft palate incision at the junction of the soft and hard palates. After hemostasis, an endoscope was inserted into the nasopharynx cavity, allowing the visualization of the pharyngeal opening of the ET on the posterior lateral wall of the nasal cavity. Subsequently, a specialized pusher was used to insert a balloon into ET. The balloon was inflated, maintained at 10 bar for 2 min, and then removed. The incision in the soft palate was then sutured to ensure proper alignment. The soft palate healed well after the operation. This surgical approach is suitable for ET-related procedures in large experimental animals (e.g., miniature pigs, sheep, and dogs). The surgical procedure is simple, with a short surgical time, and wound healing is rapid. Under endoscopy, the pharyngeal opening of the ET is visible, and it is thus a good choice for procedures such as balloon dilation of the ET.

Construction of ecological network in Qujing city based on MSPA and MCR models.

With the rapid advancement of urbanization and industrialization, ecological patches within cities and towns are fragmented and ecological corridors are cut off, regional ecological security is threatened and sustainable development is hindered. Building an ecological network that conforms to regional realities can connect fragmented patches, protect biodiversity and regional characteristics, and provide scientific reference for regional ecological protection and ecological network planning. By taking Qilin District, the main urban area of Qujing City as an example, and using geospatial data as the main data source, based on morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR), this study identified ecological source areas, extracted ecological corridors, and build & optimize ecological networks. (1) All landscape types are identified based on MSPA, the proportion of core area was the highest among all landscape types, which was 80.69%, combined with the connectivity evaluation, 14 important ecological source areas were selected. (2) 91 potential ecological corridors were extracted through MCR and gravity models, there were 16 important ones. (3) The network connectivity analysis method is used to calculate the α, ß, and γ indexes of the ecological network before optimization, which were 2.36, 6.5, and 2.53, while after optimization, α, ß and γ indices were 3.8, 9.5 and 3.5, respectively. The combined application of MSPA-MCR model and ecological network connectivity analysis evaluation is conducive to improving the structure and functionality of ecological network.

Relationships among anxiety, depression, and health-related quality of life in adult epilepsy: A network analysis.

OBJECTIVE: Comorbid depression and anxiety in patients with epilepsy (PWE) are common and frequently under-treated, thus, causing poor health-related quality of life (HRQoL). However, little is known regarding the interconnections between anxious/depressive symptoms and the dimensions of HRQoL. Therefore, we conducted a network analysis to explore these relationships in detail among Chinese adult PWE. METHODS: A cohort of adult PWE was consecutively recruited from the First Affiliated Hospital of Chongqing Medical University. HRQoL, depression, and anxiety were measured with Quality of Life in Epilepsy Inventory-31, Neurological Disorders Depression Inventory for Epilepsy, and Generalized Anxiety Disorder 7-Item Scale, respectively. A regularized partial correlation network was constructed to investigate the interconnections between symptoms of anxiety/depression and the dimensions of HRQoL. We calculated expected influence (EI) and bridge expected influence (BEI) values to identify the most influential nodes. RESULTS: A total of 396 PWE were enrolled in this study, 78.1% of whom had focal onset epilepsy. The prevalence of anxiety and depression was 30.3% and 28.8%, respectively. The symptoms "frustrated" and "uncontrollable worry" had the highest EI values, whereas "emotional well-being", "seizure worry", "difficulty finding pleasure", and "nervousness or anxiety" had the highest BEI values. CONCLUSION: This study provides new insights into the relationships among anxiety, depression, and HRQoL. Critical central symptoms and bridge symptoms identified in the network might help to quickly identify PWE comorbid anxiety and depression in busy outpatient settings, thereby enabling early intervention and enhancing quality of life.