NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

BACKGROUND:Gingival thickness is an important indicator to determine gingival phenotype.The correct evaluation of gingival phenotype is helpful for the smooth going of periodontal surgery,implant implantation and orthodontic treatment.The search for a comfortable,accurate and convenient method of measuring gingival thickness has always been a research hotspot in this field. OBJECTIVE:To analyze the gingival thickness in different dental positions and to study the consistency of cone-beam computed tomography(CBCT)image and digital intraoral scanners and cone-beam computed tomography(DIS-CBCT)superimposition image for measuring gingival thickness and determining whether the gingiva is thick or thin. METHODS:Twenty volunteers(10 males and 10 females)with complete maxillary dentition were recruited.The thickness of the gingiva 2 mm below the buccal gingival margin of 160 teeth was measured by CBCT image and DIS-CBCT digital superimposition image.Gingival thickness was used to determine whether the gingiva was thick or thin.Paired t-test was used to analyze the differences in gingival thickness measured by the two methods.Pearson correlation analysis was used to evaluate the correlation between the gingival thickness results of the two methods.The intraclass correlation coefficient(ICC)and Bland-AItman chart were used to analyze the repeatability and consistency in measuring gingival thickness using the two methods.Kappa value was used to analyze the consistency in determining whether the gingiva was thick or thin using the two methods. RESULTS AND CONCLUSION:The gingival thickness measured by CBCT image and DIS-CBCT digital superimposition image was(1.47±0.39)and(1.42±0.36)mm,respectively(t=5.673,P＜0.05).Pearson correlation analysis showed that the gingival thickness measured by the two methods was positively correlated(r=0.968,P＜0.001).In the CBCT group,the values of intraobserver and interobserver ICC were 0.980-0.982 and 0.984,respectively;in the DIS-CBCT group,the values of intraobserver and interobserver ICC were 0.941-0.984 and 0.964,respectively(P＜0.001).The intergroup ICC value of gingival thickness measured by the two methods was 0.967(P＜0.001).Bland-AItman analysis showed that 4.37%(7/160)of the points measured by both methods for gingival thickness was outside the 95%limits of agreement.There were 71 cases of thick-gingiva and 89 cases of thin-gingiva measured by CBCT imaging,and 59 cases of thick-gingiva and 101 cases of thin-gingiva measured by DIS-CBCT digital superimposition image.The Kappa value of the two groups was 0.845(P＜0.001).These findings indicate that there is a significant difference in the thickness measurement of the gingiva 2 mm below the gingival margin between the CBCT group and the DIS-CBCT group,but the correlation is very strong.The repeatability and consistency of gingival thickness measurement are both high,and there is a good consistency between the two methods when used to determine whether the gingiva is thick or thin.

Objective To investigate the prognostic value of preoperative serum albumin-to-globulin ratio (AGR) and neutrophil-lymphocyte ratio (NLR) in the overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC), and to establish an individualized nomogram model and evaluate its efficacy, in order to provide a possible evaluation basis for the clinical treatment and postoperative follow-up of ESCC patients. Methods AGR, NLR, clinicopathological and follow-up data of ESCC patients diagnosed via pathology in the Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University from 2010 to 2017 were collected. The correlation between NLR/AGR and clinicopathological data were analyzed. Kaplan-Meier analysis and log-rank test were used for survival analysis. The optimal cut-off values of AGR and NLR were determined by X-tile software, and the patients were accordingly divided into a high-level group and a low-level group. At the same time, univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting OS in the ESCC patients, and a nomogram prediction model was constructed and internally verified. The diagnostic efficacy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was evaluated by decision curve analysis. Results A total of 150 patients were included in this study, including 105 males and 45 females with a mean age of 62.3±9.3 years, and the follow-up time was 1-5 years. The 5-year OS rate of patients in the high-level AGR group was significantly higher than that in the low-level group (χ2=6.339, P=0.012), and the median OS of the two groups was 25 months and 12.5 months, respectively. The 5-year OS rate of patients in the high-level NLR group was significantly lower than that in the low-level NLR group (χ2=5.603, P=0.018), and the median OS of the two groups was 18 months and 39 months, respectively. Multivariate Cox analysis showed that AGR, NLR, T stage, lymph node metastasis, N stage, and differentiation were independent risk factors for the OS of ESCC patients. The C-index of the nomogram model was 0.689 [95%CI (0.640, 0.740)] after internal validation. The area under the ROC curve of predicting 1-, 3-, and 5-year OS rate was 0.773, 0.724 and 0.725, respectively. At the same time, the calibration curve and the decision curve suggest that the model had certain efficacy in predicting survival and prognosis. Conclusion Preoperative AGR and NLR are independent risk factors for ESCC patients. High level of AGR and low level of NLR may be associated with longer OS in the patients; the nomogram model based on AGR, NLR and clinicopathological features may be used as a method to predict the survival and prognosis of ESCC patients, which is expected to provide a reference for the development of personalized treatment for patients.

Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.

The WUSCHEL related-homeobox (WOX) family is one of the plant-specific transcription factor families, playing important roles in plant growth and development. In this study, 51 WOX gene family members were identified from the genome data of Brassica juncea by searching and screening with HUMMER, Smart and other software. Their protein molecular weight, amino acids numbers, and isoelectric point were analyzed by using Expasy online software. Furthermore, bioinformatics software was used to systematically analyze the evolutionary relationship, conservative region, and gene structure of the WOX gene family. The mustard WOX gene family was divided into three subfamilies: ancient clade, intermediate clade, and WUS clade/modern clade. Structural analysis showed that the type, organization form and gene structure of the conservative domain of WOX transcription factor family members in the same subfamily were highly consistent, while there was a certain diversity among different subfamilies. 51 WOX genes are distributed unevenly on 18 chromosomes of mustard. Most of the promoters of these genes contain cis acting elements related to light, hormone and abiotic stress. Using transcriptome data and real-time fluorescence quantitative PCR (qRT-PCR) analysis, it was found that the expression of mustard WOX gene was spatio-temporal specific, among which BjuWOX25, BjuWOX33, and BjuWOX49 might play an important role in the development of silique, and BjuWOX10, BjuWOX32, and BjuWOX11, BjuWOX23 respectively might play an important role in the response to drought and high temperature stresses. The above results may facilitate the functional study of mustard WOX gene family.
Mustard Plant/genetics* ; Multigene Family/genetics* ; Transcription Factors/metabolism* ; Plants/genetics* ; Promoter Regions, Genetic ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

【Objective】 To evaluate the curative effect of posterior atlantoaxial joint release and internal fixation in treating unstable craniocervical junction malformation （UCVJM）. 【Methods】 This study retrospectively enrolled 31 patients with UCVJM， who received posterior atlantoaxial joint release and internal fixation between January 2015 and December 2018. The pre- and postoperative changes of the Japanese Orthopaedic Association （JOA） scores， the cervicomedullary angle （CMA）， the atlantodental interval （ADI） and the height above the Chamberlain line of the odontoid （H） were traced to evaluate whether clinical symptoms， compression of spinal cord， horizontal and vertical dislocation of atlantoaxial were improved postoperatively. 【Results】 The average operation duration， bleeding during operation and the average days of hospitalization were （168.38±38.21）min， （147.09±59.84）mL， and （9.54±2.81） days， respectively. None of the patients had vertebral artery or spinal cord injury during operation. JOA score， ADI， H， and CMA were （11.94±1.37） points， （2.72±1.08）mm， （3.03±0.78）mm， and （145.35±8.00）° respectively on the 6th days after operation compared with the preoperative （9.94±1.26） points， （4.96±1.60）mm， （6.89±1.36） mm and （122.16±9.58）°， with statistical differences， which indicated all indexes were improved （all P<0.001）. During 6-25 months’ follow-up， there was no internal fixation looseness or displacement and JOA score was increased to （13.16±1.19） for all the patients in the last follow-up （all P<0.001）. 【Conclusion】 The posterior atlantoaxial joint release combined with internal fixation is safe and effective for patients with UCVJM.

Three-amino acid loop extension (TALE) transcription factors play important roles in plant growth and cell differentiation. There are plenty of studies on TALE transcription factors in several model plants, but not in radish (Raphanus sativas). A genome-wide bioinformatics analysis identified 33 TALE family genes in the Xiang-Ya-Bai (XYB) radish, These genes, are distributed on nine chromosomes and all contain 4-6 exons. The 33 TALE genes in radish showed a co-linearity relationship with the 17 homologous genes in Arabidopsis thaliana. Moreover, a large number of stress response cis-elements were found in the promoter regions of these genes. Expression analysis showed that four genes in the BELL subfamily were highly expressed in roots, and two genes in the KNOX subfamily were highly expressed in shoots of bolting plants and callus. All radish TALE genes contain sequences encoding the conserved HOX domain, except for the gene RSA10037940, which is homologous to Arabidopsis KNATM. The deduced 3D structures of the TALE proteins irrespective of subtypes are highly similar. All the encoded proteins were weakly acidic and hydrophilic. The radish TALE gene family is relatively evolutionarily conserved, which was consistent with results from Arabidopsis, but quite different from that of rice. This study provides important clues for studying the biological functions of TALE transcription factors in radish.
Amino Acids ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Raphanus/metabolism* ; Transcription Factors/metabolism*

Objective:To explore the real experience and feelings of the medical and nursing staff in the Emergency Department of general hospitals in receiving patients with mental disorders, so as to provide reference for formulating corresponding interventions.Methods:From October to November 2021, a semi-structured in-depth interview was conducted with 16 Emergency Department medical and nursing staff from two Class Ⅲ general hospitals in Nanjing by objective sampling. Colaizzi method was used to analyze the data.Results:After analyzing the interview data, three themes were extracted, namely, the emotional experience in treating and nursing patients with mental disorders, the barriers to providing the best management for patients with mental disorders (barriers at the environment/resource level, barriers at the emergency medical and nursing staff level, and barriers at the patient level) , and the educational needs of receiving patients with mental disorders (improving disease awareness and mental health service ability, and changing the way of thinking) .Conclusions:The medical and nursing staff in the Emergency Department of general hospitals have different degrees of negative emotions when receiving patients with mental disorders. There are insufficient knowledge and ability and a series of barriers when providing mental health services for patients. Managers should take various measures to improve the physical and mental health of patients with mental disorders in Emergency Department.

Objective:To evaluate the relationship between spinal kindlin-1/Wnt3a signaling pathway and inflammatory response in a rat model of neuropathic pain (NP).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (SH group), NP group, kindlin-1 shRNA group (K group) and Wnt3a inhibition group (W group). NP was induced by chronic constrictive injury in anesthetized animals.At 21 days before operation, kindlin-1 shRNA adenovirus vector 10 μl was intrathecally injected in group K, and empty viral vector 10 μl was intrathecally injected in SH, NP and W groups.Wnt inhibitor IWP-2 10 μl was intrathecally injected in group W, and artificial cerebrospinal fluid 10 μl was intrathecally injected in SH, NP and K groups at 1-3 days after operation.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before operation and 4 and 7 days after operation, respectively.At the end of pain threshold measurement at 7 days after operation, the animals were sacrificed and the lumbar segments (L 4-6) of the spinal cord were obtained for determination of the contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β (IL-1β) (using enzyme-linked immunosorbent assay) and the expression of kindlin-1 and Wnt3a (by Western blot). Results:Compared with group SH, MWT was significantly decreased, TWL was shortened at 4 and 7 days after operation, and the contents of TNF-α and IL-1β in spinal cord were increased in NP, K, and W groups, the expression of kindlin-1 and Wnt3a was up-regulated in NP and W groups, and expression of Wnt3a was up-regulated in group K ( P<0.05). Compared with group NP, MWT was significantly increased and TWL was prolonged at 4 and 7 days after operation in K and W groups, the contents of TNF-α and IL-1β in spinal cord were decreased, and the expression of kindlin-1 and Wnt3a was down-regulated in group K, the contents of TNF-α and IL-1β in spinal cord were decreased, and the expression of Wnt3a was down-regulated in group W ( P<0.05), and no significant change was found in kindlin-1 expression ( P>0.05). Conclusion:Spinal kindlin-1 regulates the inflammatory response by up-regulating the expression of Wnt3a, and it is involved in the maintenance of NP in rats.

Objective:To investigate the relationship between spinal long chain noncoding RNA (lncRNA) and kindlin-1/Wnt3a signaling pathway in a rat model of neuropathic pain (NP).Methods:The experiment was performed in two parts.Experiment Ⅰ Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were selected.Rats were sacrificed, the dorsal horn of spinal cord was removed, and the primary astrocytes were extracted and cultured.Lipopolysaccharide 1 μg/ml was added to induce the activation of astrocytes for 24 h. The lncRNA binding to kindlin-1 was identified using PCR immunoprecipitation method.The localization of lncRNA FOXF1-AS1 in astrocytes was observed by fluorescence in situ hybridization, and the binding between lncRNA FOXF1-AS1 and kindlin-1 was detected by biotin-labeled magnetic bead method.Experiment Ⅱ Thirty clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation control group (group C), NP group, lncRNA FOXF1-AS1 overexpression group (group F), lncRNA FOXF1-AS1 overexpression plus kindlin-1 shRNA group (group FK) and lncRNA FOXF1-AS1 overexpression + Wnt inhibitor group (group FW). NP was induced by chronic constrictive injury in anesthetized animals.In group F, lncRNA FOXF1-AS1 overexpression lentivirus 10 μl was intrathecally injected at 28 days before operation, and vector virus 10 μl was intrathecally injected in the other groups.In FK group, kindlin-1 interfering shRNA interference adenovirus 10 μl, and vector virus 10 μl was intrathecally injected in the other groups.In group FW, Wnt inhibitor IWP-2 10 μl was intrathecally injected at 1-3 days after operation, artificial cerebrospinal fluid 10 μl was intrathecally injected at the same time point in the other groups.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before operation, at 4 days and 7 days after operation.The animals were sacrificed at the end of measurement of pain threshold at 7 days after operation, and the spinal cord tissues were taken for determination of the expression of kindlin-1, Wnt3a and glial fibrillary acidic protein (GFAP) (by Western blot) and the contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β (IL-1β) (using enzyme-linked immunosorbent assay). Results:ExperimentⅠ lncRNA FOXF1-AS1, which was expressed in the cytoplasm of astrocytes, combined with kindlin-1.Experiment Ⅱ Compared with C group, MWT was significantly decreased, TWL was shortened at 4 and 7 days after operation, the expression of kindlin-1, Wnt3a and GFAP in spinal cord was up-regulated, and the contents of TNF-α and IL-1β were increased in group NP ( P<0.05). Compared with NP group, MWT was significantly decreased, TWL was shortened at 4 and 7 days after operation, the expression of kindlin-1, Wnt3a and GFAP in spinal cord was up-regulated, and the contents of TNF-α and IL-1β were increased in F group, MWT was increased, TWL was prolonged at 4 and 7 days after operation, and the contents of TNF-α and IL-1β were decreased in group FK and group FW, the expression of kindlin-1, Wnt3a and GFAP was down-regulated in group FK, and the expression of kindlin-1 was up-regulated, and expression of Wnt3a and GFAP was down-regulated in group FW ( P<0.05). Compared with group F, MWT was significantly increased, TWL was prolonged at 4 and 7 days after operation, and the contents of TNF-α and IL-1β were decreased in group FK and group FW, the expression of spinal kindlin-1, Wnt3a and GFAP was down-regulated in group FK, and expression of Wnt3a and GFAP was down-regulated in group FW ( P<0.05). Conclusion:lncRNA FOXF1-AS1 can up-regulate kindlin-1 expression, activate Wnt3a signaling pathway, promote astrocyte activation, and then regulate inflammatory responses and is involved in the process of neuropathic pain in rats.