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Zhen Zhang,1,2 Fulin Chen,1,2 Lijun Shang1–3 1Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi Province 710069, People’s Republic of China; 2Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, Xi’an, Shaanxi Province 710069, People’s Republic of China; 3School of Chemistry and Biosciences, Faculty of Life Sciences, University of Bradford, Bradford, UK Abstract: In recent years, the reports on using nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer prevention and treatment have been on the rise. In 2017, the US Preventive Services Working Group issued primary prevention guidelines on the use of NSAIDs, especially aspirin, for cardiovascular disease and colorectal cancer, and formally established the role and status of aspirin in cancer prevention. However, the mechanism of NSAIDs on preventing cancer is still not clear. In this paper, the progress of the application of NSAIDs, especially aspirin, in the prevention and treatment of tumors in recent years is summarized, and new ideas and directions for the follow-up study are also discussed. Keywords: NSAIDs, aspirin, platelets, cancer

Traumatic brain injury (TBI), caused by mechanical impact to the brain, is a leading cause of death and disability among young adults, with slow and often incomplete recovery. Preemptive treatment strategies may increase the injury resilience of high-risk populations such as soldiers and athletes. In this work, the xanthophyll carotenoid Astaxanthin was examined as a potential nutritional preconditioning method in mice (sabra strain) to increase their resilience prior to TBI in a closed head injury (CHI) model. The effect of Astaxanthin pretreatment on heat shock protein (HSP) dynamics and functional outcome after CHI was explored by gavage or free eating (in pellet form) for 2 weeks before CHI. Assessment of neuromotor function by the neurological severity score (NSS) revealed significant improvement in the Astaxanthin gavage-treated group (100 mg/kg, ATX) during recovery compared to the gavage-treated olive oil group (OIL), beginning at 24 h post-CHI and lasting throughout 28 days (p < 0.007). Astaxanthin pretreatment in pellet form produced a smaller improvement in NSS vs. posttreatment at 7 days post-CHI (p < 0.05). Cognitive and behavioral evaluation using the novel object recognition test (ORT) and the Y Maze test revealed an advantage for Astaxanthin administration via free eating vs. standard chow during recovery post-CHI (ORT at 3 days, p < 0.035; improvement in Y Maze score from 2 to 29 days, p < 0.02). HSP profile and anxiety (open field test) were not significantly affected by Astaxanthin. In conclusion, astaxanthin pretreatment may contribute to improved recovery post-TBI in mice and is influenced by the form of administration.

Despite advances in the treatment of hormone-refractory prostate cancer (HRPC) with docetaxel chemotherapy as evidenced by the TAX 327 and SWOG 99-16 trials, therapeutic options remain limited in patients with cancer that progresses while they are receiving hormone manipulation and chemotherapy. Targeted therapies against receptor tyrosine kinases of the ErbB family have shown some promise in the treatment of HRPC; however, patient characteristics defining susceptibility to ErbB-targeted therapies remain unknown in HRPC and limits their efficacy in the clinic. Targeted inhibition of downstream pathways, namely mammalian target of rapamycin (mTOR) may prove to be important in the treatment of HRPC because of the prevalence of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss, and it has been shown preclinically that mTOR inhibition reverses the phenotype of PTEN loss. Further investigation is necessary for the targeted inhibition of receptor tyrosine kinases and mTOR in HRPC. However, these classes of drugs may prove efficacious as tumoricidal agents or as chemo- and radiosensitizers. [ABSTRACT FROM AUTHOR]

Rab 25 is a small GTPase belonging to the RAS (rat sarcoma) superfamily. It is expressed in epithelial cells only and serves as a regulator of various intracellular signaling pathways. As a key player in in cell regulation, Rab 25 has been shown by research to function mainly as an oncogene in various cancers including breast cancer and ovarian cancer. However, Rab 25 has also been reported to be a tumor suppressor in cancer types such as colorectal cancer. A lot of research has been done about Rab 25 in recent years. This review is an overview of Rab 25, focusing on their role in human diseases such as cancer.

This paper examines how employees’ career aspirations benefit organizations, i.e., contribute to strengthening organizational capabilities and connections, by means of two aspects of contemporary work: proactive and relational. Data were collected from alumni of a public university in Amsterdam, the Netherlands, in two waves with a 1-year time lag. The results showed that employees with career aspirations strengthen: (a) organizational capabilities; and (b) organizational connections through their instrumental and psychosocial relationships. Interestingly, although employees’ career aspirations were positively associated with taking charge, we did not find that taking charge mediates the relationship between career aspirations and employees’ individual contributions to organizational capabilities. This study is the first to examine how individual career aspirations benefit organizations, and it discusses the results in light of their novel contributions to theory and practice.

A new substituted Hqnal ligand, Hqnal-5-Br q , and four resulting Fe III complexes [Fe(qnal-5-Br q ) 2 ]A·sol (A = NO 3 - , sol = CH 3 OH 1; A = ClO 4 - , sol = CH 3 OH 2; A = OTf - , sol = 2CH 3 OH·H 2 O 3; and A = NTf 2 - , sol = CH 2 Cl 2 4; Hqnal-5-Br q = N -(5-bromo-8-quinolinyl)-2-hydroxynaphthaldimine), have been synthesized and characterized. All four complexes, despite having different anions, adopt similar 1D [Fe(qnal-5-Br q ) 2 ] + cation chains linked by orthogonal π⋯π interactions. These chains are further connected to form 2D and 3D structures by other supramolecular interactions. Complexes 1-3 all exhibit abrupt spin crossover behaviors, with the transition temperatures being 230, 189, and 185 K, respectively, while complex 4 is in a high-spin state. The influence of solvents on spin crossover properties was assessed via magnetic measurements on the desolvated samples. Following desolvation, while complexes 1 and 2 show slight variations in their transition temperatures, complexes 3 and 4 undergo significant changes in their magnetic profiles. Desolvation in complex 3 leads to either a HS state or a very incomplete hysteretic transition with a low transition temperature for different sample batches. In contrast, the gradual desolvation in complex 4 leads to diminished solvent residues and progressive transition from a stable HS state to an SCO-active state.

Background: Schools are both learning environments for students and workplaces for faculty. Recognizing the role of organizational factors in staff health in school environments, the study aimed to explore which factors, including transformational leadership, teachers' perceived management support and HPS accreditation awards, were most associated with promoting a healthy lifestyle for teachers., Methods: A cross-sectional study was undertaken of 137 elementary schools in 2014, involving 433 directors and 2090 teachers. Data were collected using an anonymous structured questionnaire. Hierarchical linear modeling was used to analyze both teacher- and school-level factors associated with health-promoting lifestyles., Results: There was a significant positive correlation between teachers' overall health-promoting lifestyle profile (HPLP-II) scores and both perceived management support (coefficient = .98, p < .001) and transformational leadership (coefficient = .38, p = .039). All 6 HPLP-II subscales also showed significant positive correlations with perceived management support (coefficients .12-.24, p < .001)., Conclusion: Supporting a healthy working atmosphere and strong principal transformational leadership are keys to enhancing teachers' health-promoting lifestyles. Future research could explore how transformational leadership and management support influence teachers' health behaviors and identify effective strategies and interventions., (© 2024 American School Health Association.)

Background: Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings., Methods: Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP)., Results: The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029)., Conclusion: The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants' outcomes by facilitating timely clinical decisions., (© 2024. The Author(s).)

Dogs have played an outsized role in the field of behavioral genetics since its earliest days. Their unique evolutionary history and ubiquity in the modern world make them a potentially powerful model system for discovering how genetic changes lead to changes in behavior. Genomic technology has supercharged this potential by enabling scientists to sequence the DNA of thousands of dogs and test for correlations with behavioral traits. However, fractures in the early history of animal behavior between biological and psychological subfields may be impeding progress. In addition, canine behavioral genetics has included almost exclusively dogs from modern breeds, who represent just a small fraction of all dog diversity. By expanding the scope of dog behavior studies, and incorporating an evolutionary perspective on canine behavioral genetics, we can move beyond associations to understanding the complex interactions between genes and environment that lead to dog behavior.

Background: Workplace violence is a serious safety hazard in the healthcare sector and has attracted much attention worldwide, especially for nursing staff. Equipping nursing personnel with protective capabilities for workplace violence can reduce the risk they face in work settings. This study explored scenarios of common violent patient-nurse conflicts in the workplace of hospital nursing staff and their capabilities for de-escalating such conflicts., Methods: We used a qualitative content analysis for this study. Qualitative interviews were conducted with 21 nurses in two teaching hospitals in New Taipei City, Taiwan, until data saturation was reached. The data were transcribed, encoded, and analyzed and similar concepts were grouped under the same category., Results: Four categories of workplace violence scenarios common to hospital nursing staff were identified: unreasonable requests, caring for high-risk patients, long waiting times for medical consultation, and close contact when caring for patients. Two protective capabilities were recognized: communication and interpersonal capabilities and problem-solving skills. Each scenario may require a different combination of abilities., Conclusion: Our findings suggest that a violence-prevention training program could be designed for various workplace violence scenarios to enhance nurses' abilities to de-escalate workplace violence in hospitals., (© 2024. The Author(s).)

Objective: To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma (SCNSL)., Methods: Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected. A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival. Multivariate logistic regression analysis was used to explore the adverse prognostic factors., Results: Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research. Their 2-year overall survival (OS) rate was 46.01% and median survival time was 18.1 months. The 2-year OS rates of HD-MTX group and TMZ group were 34.3% and 61%, median survival time were 8.7 and 38.3 months, and median progression-free survival time were 8.1 and 47 months, respectively. Multivariate logistic regression analysis showed that age, sex, IPI, Ann Arbor stage were correlated with patient survival time. The median survival time of patients with CD79B, KMT2D, CXCR4, ERBB2, TBL1XR1, BTG2, MYC, MYD88, and PIM1 mutations was 8.2 months, which was lower than the overall level., Conclusion: HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

Grating emitters are the key component used in silicon photonic beam steerers to create light emission and allow dispersion-based steering. Conventional grating emitters are inefficient due to bidirectional emission, and their angular dispersion is only on the order of 0.1°/nm. In this paper, we develop unidirectional grating emitters by choosing a top cladding material with a refraction index higher than that of the bottom cladding. The refractive index difference allows the phase-matching condition to be satisfied only for the upward diffraction. We demonstrate experimentally grating emitters with a directionality of 83% and an angular dispersion of 0.79°/nm. These grating emitters have a simple device structure compatible with the standard silicon photonic platform.

Based on the differences in targeted energy metabolomics, intestinal barrier protein expression, and glucose transport,the synergistic mechanism of Coptidis Rhizoma(CR) processed with Euodiae Fructus(ECR) on ulcerative colitis(UC) was explored.Mice were administered 4% dextran sulfate sodium to induce UC model, and then randomly divided into a model group, a CR group,and an ECR group. After 14 days of treatment, the therapeutic effect of processing on UC was assessed through histopathology of colon tissue and inflammatory indexes. Targeted energy metabolomics analysis was performed to evaluate the effect of processing on colon tissue energy metabolism. Molecular docking was carried out to predict the binding affinity of energy metabolites with intestinal barrier tight junction protein Claudin and glucose transporter 2(GLUT2). In vivo unidirectional intestinal perfusion experiments in rats were conducted to evaluate the effect of processing on intestinal glucose transport. The results showed that both CR and ECR could repair colon tissue damage in UC mice, downregulate tissue inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)levels, with the efficacy of ECR being superior to CR. Processed products significantly upregulated levels of multiple metabolites in colon tissue glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation, among which the upregulated levels of 1,6-diphosphate fructose and acetyl coenzyme A could bind well with Claudin and GLUT2. Additionally, the processed product also increased the expression of GLUT2 and enhanced glucose transport activity. This study suggests that ECR may enhance glucose transport to improve colon energy metabolism, promote barrier repair, and exert synergistic effects through processing.

While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact of preanalytical factors such as the timing and anatomical location of blood draw is not well understood. To address this gap, we leveraged pet dogs with spontaneous cancer as a model system, as their compressed disease timeline facilitates rapid diagnostic benchmarking. Key liquid biopsy metrics from dogs were consistent with existing reports from human patients. The tumor content of samples was higher from venipuncture sites closer to the tumor and from a central vein. Metrics also differed between lymphoma and non-hematopoietic cancers, urging cancer-type-specific interpretation. Liquid biopsy was highly sensitive to disease status, with changes identified soon after post chemotherapy administration, and trends of increased tumor fraction and other metrics observed prior to clinical relapse in dogs with lymphoma or osteosarcoma. These data support the utility of pet dogs with cancer as a relevant system for advancing liquid biopsy platforms., Competing Interests: Competing interests: EKK, CAL, and CP are members of The One Health Company advisory board. CAL is an advisor to Merck Animal Health. CP is an employee of Precede Biosciences.

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M ( 1 ) and N ( 2 ), along with three known ones ( 3 - 5 ). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1 - 4 showed middle cytotoxicity against MCF-7 cells with IC 50 values range of 68.1 ∼ 87.32 μM. Compounds 1 - 5 displayed obvious antioxidant activity with the IC 50 values range of 0.86 ∼ 5.78 mg/mL.

Objective: To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes. Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias. Results: A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio ( OR )=1.34, 95% confidence interval ( CI ): 1.17-1.53] and intrahepatic cholestasis ( OR =2.48, 95% CI : 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia ( OR =1.49, 95% CI : 1.20-1.86) and preterm birth ( OR =1.22, 95% CI : 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Conclusion: Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.

Rice gluten, as the hydrophobic protein, exhibits restricted application value in hydrophilic food, which may be enhanced through interaction with soybean 11S globulin, characterized by favorable functional properties. This study aims at revealing their interaction mechanism via multi-spectroscopy and molecular dynamics simulation. The formation and structural change of rice glutelin-soybean 11S globulin complexes were detected using fluorescence, ultra-violet and circular dichroism spectra. The addition of 11S globulin increased the contents of α-helix, β-turn and random coil, but decreased β-sheet content, and the change in secondary structure was correlated with particle size. Moreover, exposure of hydrophobic groups and formation of disulfide bonds occurred in the complexes. Molecular dynamics simulation verified these experimental results through analyses of root mean square deviation and fluctuation, hydrogen bond, secondary structure, and binding free energy analysis. This study contributes to expounding the interaction mechanism of protein and protein from the molecular level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Using a quinoline substituted Qsal ligand, Hqsal-5-Br q (Hqsal-5-Br q = N-(5-bromo-8-quinolyl)salicylaldimine), four Fe III complexes, [Fe(qsal-5-Br q ) 2 ]A·CH 3 OH (Y = NO 3 - ( 1 NO3 ), BF 4 - ( 2 BF4 ), PF 6 - ( 3 PF6 ), OTf - ( 4 OTf ), were prepared and characterized. Structure analysis revealed that complex 2 BF4 contained two species ( 2 BF4 ( P 1 ̅) and 2 BF4 ( C 2/ c )). In these compounds except 3 PF6 , the [Fe(qsal-5-Br q ) 2 ] + cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3 PF6 , a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1 NO3 and 2 BF4 ( P 1 ̅) displayed abrupt hysteretic SCO with the transition temperature T 1/2 ↓ = 235 K, T 1/2 ↑ = 240 K for 1 NO3 and T 1/2 ↓ = 230 K, T 1/2 ↑ = 235 K for 2 BF4 ( P 1̅ ), while compounds 3 PF6 and 4 OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1 NO3 and 2 BF4 show a gradual SCO, desolvated 3 PF6 undergoes a two-step SCO, and desolvated 4 OTf exhibits a hysteretic transition. Overall, this work reported the Fe III -SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting Fe III -SCO materials.

Introduction: Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain., Methods: Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery., Results: DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure)., Discussion: Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Barbe, Chen, Loomis, Harris, Kim, Xie, Hilliard, McGonagle, Bailey, Gares, Van Der Bas, Kalicharan, Holt-Bright, Stone, Hodges and Klyne.)

Background: Aboriginal older adults residing in remote areas have poor oral function due to inadequate access to healthcare services. Lay health advisor (LHA) strategies can fill capacity shortages of healthcare professionals in rural communities and increase population acceptance of health care or healthy behaviours., Objective(s): To evaluate the effectiveness the LHA program on oral function and oral health-related quality of life (OHRQoL) among older adults in aboriginal community., Methods: Participants were randomly assigned to an experimental group (EG; n = 122) and a control group (CG; n = 118). All participants performed oral exercises, and the EG received additional one-on-one 30-min lessons by an LHA over 4 weeks. Data were collected through face-to-face interview and oral examination. The generalized estimating equation model was used to analyse changes in outcomes over time., Results: The EG exhibited significantly greater improvement in swallowing (β = .63) at the 6-month follow-up and in masticatory performance (β = .52) and pronunciation of the syllable/pa/ (β = 2.65) at the 2-week follow-up than the CG did. The EG had a significantly lower plaque control record (β = -.14) and plaque index (β = -.30) at the 3-month follow-up than the CG did. Moreover, the OHRQoL was significantly increased at 6-months follow-up in the EG (p = .010)., Conclusion: The LHA program had positive effects on chewing, swallowing and plaque control in aboriginal older adults. LHA group also experienced positive long-term effect on OHRQoL after intervention., (© 2024 John Wiley & Sons Ltd.)

Objective To develop and verify the sample size formulas for quantitative data consistency evaluation based on the least square regression method. Methods According to the principle of least square regression-based quantitative consistency evaluation,statistical inference,and formula derivation,we developed the formulas for calculating sample size based on regression constant and regression coefficient.Furthermore,the accuracy of the formulas was verified by the data of three examples,and the results were compared with those of the sample size formula established based on the Bland-Altman(BA)method. Results The sample size formulas for regression-based quantitative consistency evaluation were deduced,and the accuracy of the formulas was verified by three examples.In addition,the results obtained with this formula had differences compared with those of the sample size formula established based on the BA method.Furthermore,consistent conclusions could be obtained by regression analysis and BA analysis with the sample size calculated with the regression method.However,with the sample size calculated based on the BA method,the consistency conclusion of regression analysis and BA analysis was sometimes not valid. Conclusion A sample size formula for quantitative consistency evaluation based on the regression method was proposed for the first time,which provided methodological support for the research in this field.

Background: The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment., Aim: To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC., Methods: In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level ( α ) was 0.05, and a two-sided P < 0.05 was considered statistically significant., Results: The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ 2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ 2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage ( χ 2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite ( χ 2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD ( r = -0.601, P < 0.001), whereas VEGF was not significantly different ( r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF ( r = -0.297, P < 0.05; r = -0.548, P < 0.05 ), while VEGF expression intensity was positively related to CD31-MVD ( r = 0.421, P = 0.002)., Conclusion: It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions, including colorectal adenoma. Screening colonoscopy frequently reveals chicken skin mucosa (CSM; white or yellow-white speckled mucosa) surrounding colorectal polyps, caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors. CSM-positive colorectal polyps are associated with various diseases; however, their prognosis varies greatly. Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps. Improved imaging is required to diagnose and treat CSM-positive colorectal polyps., Aim: To highlight the clinical significance of CSM surrounding colorectal polyps and clarify the associated treatment for endoscopists., Methods: This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy. All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system. Based on the pathological results, patients were classified as non-neoplastic polyps (five juvenile polyps), neoplastic polyps, non-invasive high-grade neoplasia (NHGN), or submucosal invasive carcinoma (SM stage cancer). We analyzed and compared the clinical features, suspected risk factors for malignant transformation of neoplastic polyps, and early infiltration of submucosal carcinoma., Results: The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps. Most NHGN polyps had a deeper red mucosal color. On logistic regression analyses, diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps. Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM; type 2 CSM was more common in neoplastic polyps. Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer. Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months. No tumor recurrence was found during either partial or complete endoscopic resection of the CSM., Conclusion: CSM-positive colorectal polyps > 1 cm in diameter or with deeper red mucosa may be related to NHGN. Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions., Aim: To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen., Methods: Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety., Results: The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response., Conclusion: Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P&lt;0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t&#95;(1/2) and K&#95;e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Background: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated., Purpose: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology., Study Design: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays., Methods: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and β-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice., Results: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/β-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity., Conclusion: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis., Competing Interests: Declaration of Competing Interest The Authors have no relevant interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023. Published by Elsevier GmbH.)