Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 × 10-7, which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10-6 circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents.

Adiponectin receptors agonist alters microbiota to improve implant osseointegration in diabetic mice.

OBJECTIVE: Estimate the impact of Adiponectin receptors agonist (AdipoRon) on dental implant osseointegration in alveolar bone and explore the possible mechanism between saliva microbiota and AdipoRon in diabetic mice. MATERIALS AND METHODS: Sixty C57BL/6 mice (male, 8 weeks old) were divided randomly into four groups according to different doses of AdipoRon: normoglycemic control group; DM control group; DM with a low dose of AdipoRon (5 mg/kg/day); and DM with a high dose of AdipoRon (50 mg/kg/day). Then, dental implants were placed in the palatal root socket in the first molar extraction mouse model. Micro-computed tomography, histology examination, immunohistochemical staining, and oral microbiota were explored to evaluate implant osseointegration. RESULTS: AdipoRon treatment at 50 mg/kg markedly promoted dental implant osseointegration in diabetic mice, but AdipoRon treatment at 5 mg/kg was not effective. Moreover, distinct differences in the oral microbiota composition were shown between the diabetic mice and diabetic mice treated with AdipoRon at 50 mg/kg. CONCLUSION: AdipoRon treatment at 50 mg/kg in diabetic mice could significantly increase dental implant osseointegration. The salivary microbiota might participate in the accelerated osseointegration progress of dental implants in AdipoRon treatment.

Butyrate improves recovery from experimental necrotizing enterocolitis by metabolite hesperetin through potential inhibition the PI3K-Akt pathway.

Necrotizing enterocolitis (NEC) is one of the most common and serious intestinal illnesses in newborns and seriously affects their long-term prognosis and survival. Butyrate is a short-chain fatty acid that can relieve intestinal inflammation, but its mechanism of action is unclear. Results from an in vivo neonatal rat model has shown that butyrate caused an improved recovery from NEC. These protective effects were associated with the metabolite of hesperetin, as determined by metabolomics and molecular biological analysis. Furthermore, transcriptomics combined with inhibitor assays were used to investigate the mechanism of action of hesperetin in an in vitro NEC model (IEC-6 cells exposed to LPS) to further investigate the mechanism by which butyrate attenuates NEC. The transcriptomics analysis showed that the PI3K-Akt signaling pathway was involved in the anti-NEC effect of hesperitin. Subsequently, the results using an inhibitor of PI3K (LY294002) indicated that the suppression could be explained by the hesperetin-induced expression of tight junction (TJ) proteins by potentially blocking the PI3K-Akt signaling pathway. In summary, the present study demonstrated that butyrate could improve recovery from NEC with a hesperetin metabolite, causing potential inhibition of the phosphorylation of the PI3K-Akt signaling pathway, resulting in the increased expression of TJ proteins. These findings reveal a potential new therapeutic pathway for the treatment of NEC.

Bone protective effects of the polysaccharides from Grifola frondosa on ovariectomy-induced osteoporosis in mice via inhibiting PINK1/Parkin signaling, oxidative stress and inflammation.

BACKGROUND: Polysaccharides from Grifola frondosa(GFP) have gained worldwide attention owing to their promising biological activities and potential health benefits. PURPOSE: This study aimed to investigate the effects of GFP on alleviation of osteoporosis in ovariectomized (OVX) mice and examine the underlying mechanism. METHOD: A mouse model of postmenopausal osteoporosis was established by OVX method, Forty eight C57BL/6 female mice were randomly divided into Normal group, OVX alone (Model group, n = 8), OVX + 10 mg/kg GFP (GFP-L group, n = 8), OVX + 20 mg/kg GFP (GFP-M group, n = 8), OVX + 40 mg/kg GFP (GFP-H group, n = 8), OVX + 10 mg/kg Estradiol valerate (Positive group, n = 8). RESULTS: The results showed that compared with Model group, the concentrations of interleukin (IL)-1ß, interleukin (IL)-6 and Tumor necrosis factor-α (TNF-α) were significantly reduced, the activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased, the content of myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly reduced, and the proteins levels of PINK1, Parkin, Beclin-1 and LC3-II were significantly decreased in the GFP groups. CONCLUSION: This study demonstrates that GFP alleviates ovariectomy-induced osteoporosis via reduced secretion of inflammatory cytokines, improvement in the oxidative stress status in the body, and inhibition of the PINK1/Parkin signaling pathway.

Unlocking the mysteries of milk oligosaccharides: Structure, metabolism, and function.

Milk oligosaccharides (MOs), complex carbohydrates prevalent in human breast milk, play a vital role in infant nutrition. Serving as prebiotics, they inhibit pathogen adherence, modulate the immune system, and support newborn brain development. Notably, MOs demonstrate significant variations in concentration and composition, both across different species and within the same species. These characteristics of MOs lead to several compelling questions: (i) What distinct beneficial functions do MOs offer and how do the functions vary along with their structural differences? (ii) In what ways do MOs in human milk differ from those in other mammals, and what factors drive these unique profiles? (iii) What are the emerging applications of MOs, particularly in the context of their incorporation into infant formula? This review delves into the structural characteristics, quantification methods, and species-specific concentration differences of MOs. It highlights the critical role of human MOs in infant growth and their potential applications, providing substantial evidence to enhance infant health and development.

[The Study of Recombinant Interfering Lentiviruses and Overexpressed Adenovirus Vectors Targeting Human c-Cbl Gene： Construction, Identification and Efficacy].

OBJECTIVE: To construct recombinant lentivirus and adenovirus which regulate the expression of c-Cbl gene and evaluate their efficacy. METHODS: The interference lentivirus and overexpressed adenovirus targeting human c-Cbl gene were constructed by gene recombination technology. Quantitative PCR and western blotting were used to detect the expression changes in c-Cbl gene and its transcription after leukemia cells (HL60,THP1) were infected by virus. RESULTS: Three recombinant interfering lentiviral vectors targeting human c-Cbl genes to successfully constructed and were identified by DNA sequencing, and the titers of the packaged viruses were all greater than 1×108 TU/ml. Among them, shRNA-2 lentivirus had the highest interference efficiency, and the expression of c-Cbl gene and CBL protein were decreased about 95% and 60% respectively after leukemia cells were infected with shRNA-2; In addition, the recombinant overexpression adenovirus targeting human c-Cbl gene was packaged successfully with the virus titer greater than 1×109 TU/ml. When leukemia cells were infected with adenovirus, the expression of c-Cbl gene and CBL protein were up-regulated about 10 times and 1.5 times respectively. CONCLUSION: Both recombinant interfering lentivirus and overexpression adenovirus can efficiently infect leukemia cells and affect the expressions of c-Cbl gene and CBL protein. It will lay a preliminary foundation for the subsequent study on the function of c-Cbl gene in tumor cells.

Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

To Evaluate the Value of Vertebral Body Cortical Thickness in Predicting Osteoporosis by Opportunistic CT.

BACKGROUND: In vertebrae, the amount of cortical bone has been estimated at 30-60%, but 45-75% of axial load on a vertebral body is borne by cortical bone (1). RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of vertebral body cortical thickness in predicting osteoporosis (OP) by analyzing the relationship between vertebral body cortical thickness and bone mineral density (BMD) in different age and gender groups. The optimal diagnostic cut-off value of vertebral body cortical thickness in predicting OP was analyzed. MATERIALS AND METHODS: The data of 150 patients (50-89 years old) who underwent chest or abdominal Quantitative computed tomography (QCT) scan (obtained in one scan) in our hospital from July 2021 to July 2022 were retrospectively analyzed. The average volume bone mineral density (vBMD) of L1-L2 vertebral bodies was obtained and grouped according to BMD, age, and gender. According to BMD, the patients were divided into three groups: osteoporosis, osteopenia and normal. According to age, the patients were divided into three groups: 50-59 years, 60-69 years and ≥70 years. The axial images of T11, T12 and L1 were reconstructed with 1.25 mm slice thickness by AW4.7 workstation provided by General Electric Co (GE) Company. The images were imported into the computed tomography (CT) Spine Bone Quantification System software for spine analysis, and the vertebral body cortical thickness values were obtained. CT Spine Bone Quantification System is a software for quantitative analysis and separation of cortical bone and cancellous bone. RESULTS: A total of 150 patients were enrolled in this study, including 49 patients in the osteoporosis group, 51 patients in the osteopenia group, and 50 patients in the normal group. The cortical thickness values of T11, T12 and L1 were positively correlated with BMD, and the correlation coefficient was 0.750 at T11. According to the receiver operating characteristic (ROC) curve analysis of T11, T12, L1 cortical thickness value and BMD, OP was diagnosed when T11 < 2.75 mm, T12 < 3.06 mm, and L1 < 2.67 mm. The sensitivity was 83.67%, 87.76%, 75.51%, respectively. The specificity was 79.21%, 71.29% and 90.10%, respectively, and the difference was statistically significant. CONCLUSION: Vertebral body cortical thickness is correlated with BMD and age. According to the cut-off value of different vertebral bodies, OP can be predicted when T11 < 2.75 mm or T12 < 3.06 mm or L1 < 2.67 mm.

Ultra-short cell-free DNA fragments enhance cancer early detection in a multi-analyte blood test combining mutation, protein and fragmentomics.

OBJECTIVES: Cancer morbidity and mortality can be reduced if the cancer is detected early. Cell-free DNA (cfDNA) fragmentomics emerged as a novel epigenetic biomarker for early cancer detection, however, it is still at its infancy and requires technical improvement. We sought to apply a single-strand DNA sequencing technology, for measuring genetic and fragmentomic features of cfDNA and evaluate the performance in detecting multiple cancers. METHODS: Blood samples of 364 patients from six cancer types (colorectal, esophageal, gastric, liver, lung, and ovarian cancers) and 675 healthy individuals were included in this study. Circulating tumor DNA mutations, cfDNA fragmentomic features and a set of protein biomarkers were assayed. Sensitivity and specificity were reported by cancer types and stages. RESULTS: Circular Ligation Amplification and sequencing (CLAmp-seq), a single-strand DNA sequencing technology, yielded a population of ultra-short fragments (<100 bp) than double-strand DNA preparation protocols and reveals a more significant size difference between cancer and healthy cfDNA fragments (25.84 bp vs. 16.05 bp). Analysis of the subnucleosomal peaks in ultra-short cfDNA fragments indicates that these peaks are regulatory element "footprints" and correlates with gene expression and cancer stages. At 98 % specificity, a prediction model using ctDNA mutations alone showed an overall sensitivity of 46 %; sensitivity reaches 60 % when protein is added, sensitivity further increases to 66 % when fragmentomics is also integrated. More improvements observed for samples representing earlier cancer stages than later ones. CONCLUSIONS: These results suggest synergistic properties of protein, genetic and fragmentomics features in the identification of early-stage cancers.

Obesity and temporomandibular joint disorders: a systematic review and meta-analysis.

BACKGROUND: Temporomandibular joint disorders (TMD) is the most common non-dental pain complaint in the maxillofacial region, which presents a variety of symptoms and signs, including temporomandibular joints (TMJ) and masticatory muscle pain, joint noise, tinnitus, headaches, irregular or restricted mandibular function, masticatory difficulty, and restricted mouth opening. When comes to the relationship between obesity and TMD, it has remained controversial and inconsistent, therefore, we first conducted this meta-analysis to estimate the unclear relationship between obesity and TMD. METHODS: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Subjects were divided into five groups according to BMI level in this study, including the normal weight group: 18.5 ≤ BMI < 25, overweight group: 25 ≤ BMI < 30, obesity group: BMI ≥ 30, control group: BMI < 25, and overweight and obesity group: BMI ≥ 25. Statistics analyses were conducted using Stata (15.0). The number of PROSPERO was CRD42022368315. RESULTS: Eight studies were included in this study, and six articles with a total of 74,056 participants were synthesized for meta-analysis. Compared to normal weight individuals, overweight and obesity together decreased the risk of TMD (OR = 0.66, 95% CI = 0.46-0.95), and it was significantly decreased by obesity alone (OR = 0.58). Moreover, it was lower in obesity compared with control subjects (OR = 0.83, 95% CI = 0.73-0.94). Furthermore, in overweight and obese individuals, it was much lower in obesity than in overweight (OR = 0.82, 95% CI = 0.71-0.94). CONCLUSIONS: Obesity is not a risk factor for TMD, and maybe a protective factor for TMD, of which patients with larger BMI are less likely to suffer from TMD pain. Therefore, the value of BMI should be taken into consideration in the assessment of TMD.

Toxicological effects of micro/nano-plastics on mouse/rat models: a systematic review and meta-analysis.

Micro/nano-plastics (MNPs) are considered a heterogeneous class of environmental contaminants that cause multiple toxic effects on biological species. As the commonly used mammalian models to study the effects of MNPs with regard to their toxic effects, the mouse and rat models are making a great contribution to the disciplines of environmental toxicology and medical health. However, the toxic effects of MNPs have not been systematically summarized. Therefore, a systematic review and a meta-analysis of the toxic effects of MNPs on mouse/rat models were conducted. A total of seven main categories were established in this systematic review, and 24 subcategories were further divided according to the specific physiological significance of the endpoint or the classification of the physiological system, which covered all the selected pieces of literature. A total of 1,762 biological endpoints were found, and 52.78% of them were significantly affected. This fact indicates that there are relative factors, including the size, polymer type, concentration, and exposure time of MNPs and different sexes of mouse/rat models that could significantly affect the biological endpoints. These biological endpoints can be classified into various factors, such as the dose-response relationships between MNP concentration and physiological categories of the nervous system, growth, reproduction, digestive tract histopathology, and inflammatory cytokine level, among others. MNPs negatively affected the blood glucose metabolism, lipid metabolism, and reproductive function in mice. The reproductive function in male mice is more sensitive to the toxic effects of MNPs. These findings also provide insights into and directions for exploring the evidence and mechanisms of the toxic effects of MNPs on human health. It is clear that more research is required on the pathological mechanisms at the molecular level and the long-term effects of tissue accumulation.

Pathophysiological Association of Alzheimer's Disease and Hypertension: A Clinical Concern for Elderly Population.

Alzheimer's disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.

Oncology nursing on the move: a contemporary issue on Chinese oncology nursing in cancer care.

Cancers have become the primary cause of death among Chinese residents, seriously affecting their health and life. Oncology nursing is a specialized nursing practice focusing on cancer education, prevention, screening, early detection, and palliative and hospice care. China has made tremendous progress in developing oncology nursing. However, to ensure more individuals can get cancer care, the country's healthcare system still confronts several problems in oncology nursing that need to be addressed to ensure that more individuals can receive cancer care. This article reviews the current development of oncology nursing in China, especially in pain symptom control, palliative care, end-of-life care, education and training. The challenges faced in oncology nursing in China and the suggestions for developing oncology nursing in China are also discussed and proposed in this review. The growth of research on oncology nursing by Chinese nursing scholars and concerned policymakers is anticipated to ultimately improve oncology nursing and the quality of life of patients with cancer in China.

Sorafenib regulates c-CBL gene-mediated chemoresistance in acute myeloid leukemia cells.

Chemotherapeutic regimens containing sorafenib are widely used in salvage treatment for patients with relapsed and refractory acute leukemia, especially those with FLT3-ITD mutations. However, the therapeutic effects in individuals are heterogeneous, and the effective maintenance period is relatively short. Our clinical analysis showed patients with high c-kit (CD117) expression in leukemia cells generally had a better response to sorafenib, but the reason for this finding was not clear. c-kit (CD117) is a receptor tyrosine kinase, and its signal inactivation and hydrolytic metabolism are regulated by the CBL protein, a Ring finger E3 ubiquitin ligase, encoded by the c-CBL gene. And we also found that the c-CBL gene expression in refractory and relapsed patients was significantly lower than that in healthy hematopoietic stem cell donors. Therefore, we assumed that there is a relationship among c-CBL gene function, high expression of c-kit (CD117) and a better clinical response to sorafenib. To confirm this hypothesis, we packaged interfering lentiviruses and overexpressed adenoviruses targeting the c-CBL gene respectively, and infected leukemia cell lines with these viruses to regulate the expression of the c-CBL gene, and observed the subsequent changes of these cells in various biological behaviors. Our results showed when the c-CBL gene was silenced, the cells proliferation was accelerated, drug sensitivity to cytarabine or sorafenib was decreased, and apoptosis ratio was decreased. And all these phenomena were reversed when the gene was overexpressed, which confirmed the expression of c-CBL gene was related to drug resistance in leukemia cells. At last, we explored the possible molecular mechanisms underlying these phenomena.

Correlation Analysis between Residual Pain after Vertebral Augmentation and the Diffusion Distribution of Bone Cement: A Retrospective Cohort Study.

Objective: To explore the influence and potential factors of the bone cement dispersion state on residual pain after vertebral augmentation. Methods: The cases included in this retrospective cohort study were patients treated with vertebral augmentation (VA) for osteoporotic vertebral compression fractures (OVCFs) between July 2018 and June 2021. According to the type of cement diffusion distribution, the patients were divided into a sufficient diffusion group (Group A) and an insufficient diffusion group (Group B). The differences in the baseline data, visual analog scale (VAS), Oswestry disability index score (ODI), injured vertebral height (IVH), and local kyphosis angle (LKA) between the two groups were analyzed. Assessments were performed preoperatively on the 2nd day postoperation and at the last follow-up. The imaging data of injured vertebrae were accurately reconstructed by a GE AW4.7 workstation, and the differences in the vertebral body volume, bone cement volume, and bone cement volume ratio were compared between the groups. Result: After screening, 36 patients were included. (1) The postoperative VAS and ODI scores of the two groups were significantly improved compared with the preoperative scores. (2) On the 2nd day postoperation and the last follow-up, the VAS and ODI scores of Group A were significantly different from those of Group B, and Group A outperformed Group B. (3) The IVH and LKA of the two groups were improved after the operation, and no significant difference was found between the groups. (4) Significant differences were found in the bone cement volume and bone cement volume ratio between the groups, and Group A was larger than Group B. Conclusions: Sufficient bone cement diffusion can reduce residual pain after vertebral augmentation.

The Milk Active Ingredient, 2'-Fucosyllactose, Inhibits Inflammation and Promotes MUC2 Secretion in LS174T Goblet Cells In Vitro.

In several mice inflammatory models, human milk oligosaccharides (HMOs) were shown to protect the intestinal barrier by promoting mucin secretion and suppressing inflammation. However, the functions of the individual HMOs in enhancing mucin expression in vivo have not been compared, and the related mechanisms are not yet to be clarified. In this study, we investigated the modulatory effects of 2'-fucosyllactose (2'-FL), 3'-sialyllactose (3'-SL), galacto-oligosaccharide (GOS) and lactose (Lac) on goblet cells' functions in vitro. The appropriate dosage of the four chemicals was assessed in LS174T cells using the CCK-8 method. Then they were supplemented into a homeostasis and inflammatory environment to further investigate their effects under different conditions. Mucin secretion-related genes, including mucin 2 (MUC2), trefoil factor family 3 (TFF3), resistin-like ß (RETNLB), carbohydrate sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), in LS174T cells were detected using quantitative RT-qPCR. The results showed that 2'-FL (2.5 mg/mL, 72 h) was unable to increase MUC2 secretion in a steady-state condition. Comparatively, it exhibited a greater ability to improve mucin secretion under an inflammatory condition compared with GOS, demonstrated by a significant increase in TFF3 and CHST5 mRNA expression levels (p > 0.05). However, 3'-SL and Lac exhibited no effects on mucin secretion. To further investigate the underlying mechanism via which 2'-FL enhanced goblet cells' secretion function, the NOD-like receptor family pyrin domain containing 6 (NLRP6) gene, which is closely related to MUC2 secretion, was silenced using the siRNA method. After silencing the NLRP6 gene, the mRNA expression levels of MUC2, TFF3 and CHST5 in the (2'-FL + tumor necrosis factor α (TNF-α) + NLRP6 siRNA) group were significantly decreased compared with the (2'-FL + TNF-α) group (p > 0.05), indicating that NLRP6 was essential for MUC2 expression in goblet cells. We further found that 2'-FL could significantly decrease toll-like receptor 4 (TLR4, p < 0.05), myeloid differential protein-88 (MyD88, p < 0.05) and nuclear factor kappa-B (NF-κB, p < 0.05) levels in LS174T inflammatory cells, even when the NLRP6 was silenced. Altogether, these results indicated that in goblet cells, 2'-FL exerts its function via multiple processes, i.e., by promoting mucin secretion through NLRP6 and suppressing inflammation by inhibiting the TLR4/MyD88/NF-κB pathway.

Improved fractionation method using amphipathic NDAM for the efficient separation of disinfection by-product precursors in natural organic matter.

The hydrophilic substances in natural organic matter (NOM) are the main precursor of disinfection by-products (DBPs) formed during disinfection processes. The fractionation of the components in NOM based on hydrophilicity contributes to elaborating the behavior of NOM during disinfection. However, the traditional NOM fractionation method using two hydrophobic resins of DAX-8 and XAD-4 lays emphasis on the separation of hydrophobic substances, limiting the thorough study of the hydrophilic components in NOM. In this work, the amphiphilic resin NDAM was employed as a replacement of XAD-4 to realize more thorough separation of the hydrophilic substances. Compared with the divinylbenzene (DVB) structure of XAD-4, the NDAM possesses a more hydrophilic skeleton of N-vinylpyrrolidone (NVP) and DVB which favors the adsorption of hydrophilic components in NOM. The two fractionation methods of DAX-8 + XAD-4 and DAX-8 + NDAM were applied to fractionate NOM, and the obtained fractions were characterized via fluorescence spectra, UV spectra, acid-base titration, the partition coefficients of aqueous two-phase systems(ATPs), and 1H nuclear magnetic resonance (1H-NMR). The results showed that the transphilic fractions separated by XAD-4 accounted for 11.09% of NOM, while the proportion increased to 20.33% with the method of NDAM fractionation. Besides, the hydrophilic components enriched by NDAM not only have more π-conjugated systems and more aromatic structure but also contain more oxygen-containing and nitrogen-containing functional groups. In addition, the hydrophilic fractions separated by NDAM contained more DBP precursors. The NDAM separates more NOM which can produce bromine-containing DBPs into HPIA, and the DBP productivity of HPIN is significantly higher than that of XAD-4. In general, the NOM fractionation method proposed in this study utilizing NDAM resin could fractionate the hydrophilic fractions in NOM more thoroughly, showing application potential in the analysis and control of DBPs formed from NOM.

Association between smoking and Schneiderian membrane perforation during maxillary sinus floor augmentation: A systematic review and meta-analysis.

OBJECTIVE: To estimate the association between smoking and Schneiderian membrane perforation in sinus floor augmentation. MATERIALS AND METHODS: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Data were extracted by two authors independently. The inclusion criteria were the (1) age of patients >18, (2) the number of participants >10, and (3) smoking and the patients of Schneiderian membrane perforation were accurately recorded. The risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Statistics analyses were conducted using Reman5.4.1 and Stata (15.0). The association of Schneiderian membrane perforation with smoking habits during maxillary sinus floor elevation was expressed as odds ratios (ORs) with a 95% confidence interval (95% CIs). And the I2 statistic was used to estimate statistical heterogeneity. The funnel plot and Egger's tests were used to evaluate the reliability and stability of the results. RESULTS: Of 1463 articles screened, nine studies were included in our systematic review, and eight were synthesized for meta-analysis. Eight were retrospective observational studies and one was a clinical trial, with a total of 1424 patients included. The nine studies were proved as high quality according to the NOS. There was no significant publication bias in the studies (p = 0.827). A random-effects model was used because of differences in the adopted methodologies (p = 0.39, I2  = 5%). During maxillary sinus augmentation, smoking and Schneiderian membrane perforation were associated (odds ratios, 1.58 [95% CI, 1.10-2.25]). CONCLUSION: Smoking increased the risk of membrane perforation in maxillary sinus floor augmentation. Our evaluation was limited by the poor reporting of the number of cigarettes smoked per day (PROSPERO number was CRD42022306570).

Association between Lipoprotein(a) and diabetic nephropathy in patients with type 2 diabetes.

Background: Diabetic nephropathy (DN) is one of the most prevalent and severe microvascular complications of type 2 diabetes (T2DM). However, little is currently known about the pathogenesis and its associated risk factors in DN. The present study aims to investigate the potential risk factors of DN in patients with T2DM. Methods: A total of 6,993 T2DM patients, including 5,089 participants with DN and 1,904 without DN, were included in this cross-sectional study. Comparisons between the two groups (DN vs. non-DN) were carried out using Student's t-test, Mann-Whitney U-test, or Pearson's Chi-squared test. Spearman's correlation analyses were performed to assess the correlations of serum lipids and indicators of renal impairment. Logistic regression models were applied to assess the relationship between blood lipid indices and the presence of DN. Results: T2DM patients with DN were older, and had a longer duration of diagnosed diabetes compared to those without DN. Of note, the DN patients also more likely develop metabolic disorders. Among all serum lipids, Lipoprotein(a) [Lp(a)] was the most significantly correlated indicators of renal impairment. Moreover, univariate logistic regression showed that elevated Lp(a) level was associated with an increased risk of DN. After adjusted for confounding factors, including age, gender, duration of T2DM, BMI, SBP, DBP and lipid-lowering drugs usage, Lp(a) level was independently positively associated with the risk of DN [odds ratio (OR):1.115, 95% confidence interval (CI): 1.079-1.151, P=6.06×10-11]. Conclusions: Overall, we demonstrated that serum Lp(a) level was significantly positively associated with an increased risk of DN, indicating that Lp(a) may have the potential as a promising target for the diagnosis and treatment of diabetic nephropathy.

Lactoferrin Inhibits the Development of T2D-Induced Colon Tumors by Regulating the NT5DC3/PI3K/AKT/mTOR Signaling Pathway.

Although increasing evidence shows the association between type 2 diabetes (T2D) and colorectal cancer, the related mechanism remains unclear. This study examined the suppressive effect of lactoferrin (LF) on the development of T2D-induced colon cancer. First, a co-cultured cell model consisting of NCM460 and HT29 cells was constructed to mimic the progression of T2D into colon cancer. The migration ability of NCM460 cells increased significantly (p < 0.05) after cultivation in HT29 cell medium (high glucose), while LF suppressed the progression of T2D to colon cancer by regulating the 5'-nucleotidase domain-containing 3 (NT5DC3) protein and the PI3K/AKT/mTOR signaling pathway in diabetic BALB/c mice and in cell models. A mutation assay of the phosphorylation site in the NT5DC3 protein and a surface plasmon resonance (SPR) protein binding test were performed to further ascertain a mechanistic link between LF and the NT5DC3 protein. The results indicated that LF specifically bound to the NT5DC3 protein to activate its phosphorylation at the Thr6 and Ser11 sites. Next, metabolic-specific staining and localization experiments further confirmed that LF acted as a phosphate donor for NT5DC3 protein phosphorylation by regulating the downstream metabolic pathway in T2D-induced colon tumors, which was specifically accomplished by controlling Thr6/Ser11 phosphorylation in NT5DC3 and its downstream effectors. These data on LF and NT5DC3 protein may suggest a new therapeutic strategy for cancer prevention, especially in T2D patients susceptible to colon cancer.