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1.
World J Gastrointest Surg ; 16(8): 2662-2670, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39220080

ABSTRACT

BACKGROUND: Patients with rectal cancer undergoing radical resection often have poor postoperative recovery due to preoperative fasting and water deprivation and the removal of diseased tissue, and have a high risk of complications. Therefore, it is of great significance to apply appropriate rehydration regimens to patients undergoing radical resection of rectal cancer during the perioperative period to improve the postoperative outcomes of patients. AIM: To analyze the effects of goal-directed fluid therapy (GDFT) with a preoperative glucose load regimen on postoperative recovery and complications in patients undergoing radical resection for rectal cancer. METHODS: Patients with rectal cancer who underwent radical resection (n = 184) between January 2021 and December 2023 at our hospital were randomly divided into either a control group or an observation group (n = 92 in each group). Both groups received a preoperative glucose load regimen, and routine fluid replacement and GDFT were additionally implements in the control and observation groups, respectively. The operative conditions, blood levels of lactic acid and inflammatory markers, postoperative recovery, cognitive status, hemodynamic indicators, brain oxygen metabolism, and complication rates were compared between the groups. RESULTS: The colloidal fluid dosage, total infusion, and urine volume, as well as time to first exhaust, time to food intake, and postoperative length of hospital stay, were lower in the observation group (P < 0.05). No significant differences were observed between the two groups in terms of operation time, bleeding volume, crystalloid liquid consumption, time to tracheal extubation, complication rate, heart rate, or mean arterial pressure (P > 0.05). Compared with the control group, in the observation group the lactic acid level was lower immediately after the surgery (P < 0.05); the Mini-Mental State Examination score was higher on postoperative day 3 (P < 0.05); the pulse pressure variability (PPV) was lower at 30 min after pneumoperitoneum (P < 0.05), though the differences in the PPV of the two groups was not significant at the remaining time points (P > 0.05); tumor necrosis factor-α and interleukin-6 levels were lower on postoperative day 3 (P < 0.05); and the left and right regional cerebral oxygen saturation was higher immediately after the surgery and 30 min after pneumoperitoneum (P < 0.05). CONCLUSION: GDFT combined with the preoperative glucose load regimen is a safe and effective treatment strategy for improving postoperative recovery and risk of complications in patients with rectal cancer undergoing radical resection.

2.
Front Pediatr ; 12: 1450710, 2024.
Article in English | MEDLINE | ID: mdl-39220153

ABSTRACT

Background: Kawasaki disease (KD) is characterized as an acute febrile inflammatory disorder, which may potentially escalate into a more severe condition termed Kawasaki disease shock syndrome (KDSS). The objective of this research is to understand the clinical attributes of KDSS and to explore the predictive significance of coagulation profiles in the incidence of KDSS. Method: Patients with Kawasaki disease (KD) were prospectively enrolled and divided into the KDSS group (n = 29) and the non-KDSS group (n = 494). Multivariate logistic regression analysis was used to ascertain the relationship between coagulation profiles and KDSS. Furthermore, ROC curve analysis was conducted to evaluate the predictive value of the coagulation profile for the occurrence of KDSS. Result: Among the KDSS patients, the median age was higher and cervical lymph node involvement was greater compared to the non-KDSS group. Additionally pericardial effusion, valve regurgitation, cardiac enlargement, coronary artery lesions (CALs), and Intravenous immunoglobulin (IVIG) resistance were significantly more frequent in the KDSS group than in non-KDSS group. Notably, Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and fibrin degradation products (FDP) were significantly elevated in the KDSS group compared to the non-KDSS group. Conversely, total thrombin time (TT), fibrinogen, and antithrombin III (ATIII) activity were significantly reduced. Multivariate logistic regression analysis revealed that PT, APTT, D-dimer, and ATIII were independent risk factors for predicting KDSS occurrence. ROC curve analysis established critical values for PT, D-dimer, FDP, and ATIII as 13.45 s, 2.03 mg/L, 7.45 µg/ml, and 77.5%, respectively. Sensitivity for predicting KDSS occurrence was 76%, 79%, 83%, and 76%, while specificity was 51%, 72%, 63%, and 80%, respectively. When we performed a combined ROC curve analysis of the four indicators, we found that its predictive sensitivity was much higher. Moreover, the Delong test results showed that the AUC of the combined analysis was significantly higher than that of the individual analyses. Conclusion: Characteristic features of KDSS include older age, a greater likelihood of experiencing pericardial effusion, valve regurgitation, cardiac enlargement, CALs, and IVIG resistance. KD patients with a hypercoagulable state during the acute phase are at a higher risk of developing KDSS.

3.
Rev Cardiovasc Med ; 25(8): 309, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39228506

ABSTRACT

Background: The prognosis of Duchenne muscular dystrophy (DMD) is poor once it develops to the stage of cardiac impairment. Recent studies have demonstrated that electrocardiogram (ECG), which consists of general ECG and vectorcardiogram (VCG), retains an extremely powerful role in the assessment of patients with reduced left ventricular (LV) systolic dysfunction. However, data regarding VCG recordings in DMD and its prognostic value for reduced left ventricular ejection fraction (LVEF) of DMD have never been reported. This study aims to describe the characteristics of VCG in children with DMD and to explore the predictive value of VCG for reduced LVEF in children with DMD. Methods: A total of 306 patients with a known diagnosis of DMD confirmed by the genetic test were retrospectively enrolled at our hospital between August 2018 and August 2022. This resulted in a total study group of 486 VCG recordings. Among them, 75 DMD patients who underwent cardiac magnetic resonance (CMR) later after one year follow-up were prospectively enrolled. The trend of VCG parameters of DMD patients across the different age span were compared with age-matched normal children. Concordance statistic analysis was further performed to assess the validity of VCG parameters in predicting the occurrence of reduced LVEF in patients with DMD. Results: DMD patients have a significantly higher heart rate, R waves in V1, QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) than normal children. Concordance statistic (C-statistic) showed an area under the curve of quadrant IV in the sagittal plane of baseline was 0.704. The receiver operating characteristic (ROC) curve shows that quadrant IV in the sagittal plane of 7.57% was the optimal cutoff with a sensitivity of 53.3% and a specificity of 88.3% for predicting reduced LVEF in DMD patients. Conclusions: Our study firstly showed that QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) could be abnormal in DMD boys as early as before 5 years old. Evaluation of the myocardium by VCG in the early age to predict possible cardiac systolic dysfunction may have important implications for the ongoing management of DMD boys.

4.
Article in English | MEDLINE | ID: mdl-39230609

ABSTRACT

OBJECTIVE: We explored the use of ultrasonography in determining the minimal transverse diameter of the subglottic airway (MTDSA) for the purpose of choosing an appropriate model of reinforced cuffed endotracheal tube. METHODS: A total of 110 pediatric patients who received general anesthesia and tracheal intubation for selective surgeries at the hospital from February 2019 to February 2022 were chosen. They were then randomly assigned to three groups: 39 in the MTDSA group, 35 in the age formula group, and 36 in the height formula group. We assessed how accurately the appropriate endotracheal tube model was predicted in each group and compared their predictive performance. RESULTS: The age range of the enrolled pediatric patients was 3-6 years old. The ultrasonic measurement method demonstrated a prediction accuracy of 87.18%, while the age formula method and height formula method exhibited lower accuracy rates of 54.29% and 47.22%, respectively. Notably, the ultrasonic measurement method outperformed the other two methods significantly (P < 0.05). In the MTDSA group, 2 patients had their catheters changed during anesthesia, and the proportion of patients who changed their catheters was 5.13%. In the MTDSA group, 6 catheters were replaced, and the frequency of catheter replacement was 15.38%. In contrast, these percentages were much higher in the age formula group, at 31.43% and 45.71%, and in the height formula group, at 36.11% and 52.78%. The latter two groups had significantly higher values than the MTDSA group (P < 0.05). Regarding complications such as hoarseness, laryngeal edema, aspiration, and laryngospasm, the MTDSA group experienced a notably lower total incidence of 7.69% compared to the 37.14% in the age formula group and 41.67% in the height formula group, demonstrating statistical significance (P < 0.05). CONCLUSION: The ultrasonic measurement technique employed in MTDSA exhibits impressive precision when it comes to forecasting the specific model of a reinforced cuffed endotracheal tube for pediatric patients. This enhanced accuracy contributes significantly to minimizing the need for tube replacements during anesthesia and the associated complications. It holds immense importance in assisting clinicians in selecting the most appropriate pediatric endotracheal tube model for anesthesia induction.

5.
Front Endocrinol (Lausanne) ; 15: 1417228, 2024.
Article in English | MEDLINE | ID: mdl-39099668

ABSTRACT

Aims: Cholesterol carried in triglyceride-rich lipoproteins, also called remnant cholesterol, is increasingly acknowledged as an important causal risk factor for atherosclerosis. Elevated remnant cholesterol, marked by elevated plasma triglycerides, is associated causally with an increased risk of atherosclerotic cardiovascular disease. However, the association with all-cause mortality and cause-specific mortality is inconclusive. This study aimed to test the hypothesis that remnant cholesterol levels and plasma triglycerides are associated with increased all-cause mortality and mortality from cardiovascular disease, cancer, and other causes. Methods and results: Using a contemporary population-based cohort, 7,962 individuals from the National Health and Nutrition Examination Survey (NHANES) aged over 40 years at baseline in 2003-2015 were included. During up to 109.2 (± 1.44) months of follow-up, 1,323 individuals died: 385 individuals died from cardiovascular disease, 290 from cancer, 80 from cerebrovascular disease, and 568 from other causes. Compared with the middle tertile remnant cholesterol level, multivariable-adjusted mortality hazard ratios were 1.20 (95% confidence interval 1.02-1.40) for all-cause mortality. For the highest tertile remnant cholesterol level, multivariable-adjusted mortality hazard ratios were 1.21 (95% confidence interval 1.05,1.40). Our conclusions remained stable in subgroup analyses. Exploratory analysis of the cause of death subcategories showed corresponding hazard ratios of 1.25 (1.13-1.38) for Non-cardiovascular and Non-cerebrovascular Death for lower remnant cholesterol individuals, 1.47 (1.01-2.15) for cancer death for lower remnant cholesterol (RC) individuals, and 1.80 (1.36-2.38) for cancer death for higher RC individuals. Conclusion: RC levels were associated with U-shaped all-cause mortality. RC was associated with mortality from non-cardiovascular, non-cerebrovascular, and cancer, but not from cardiovascular causes. This novel finding should be confirmed in other cohorts.


Subject(s)
Cardiovascular Diseases , Cholesterol , Neoplasms , Nutrition Surveys , Humans , Male , Female , Middle Aged , Cholesterol/blood , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Adult , Risk Factors , Neoplasms/mortality , Neoplasms/blood , Triglycerides/blood , Aged , Cause of Death , Mortality/trends , Follow-Up Studies , United States/epidemiology , Cohort Studies
6.
Front Neurol ; 15: 1370609, 2024.
Article in English | MEDLINE | ID: mdl-39114535

ABSTRACT

Objective: Preoperative obstructive sleep apnea (OSA) is supposed to be the abnormally high occurrence of OSA the night before surgery under general anesthesia. This study aimed to evaluate the prevalence preoperative OSA using cardiopulmonary coupling (CPC) and its correlation with imbalance of sympathetic/parasympathetic nervous system. Methods: A total of 550 patients with plans to receive surgery under general anesthesia were enrolled. All patients were assigned to wear CPC on the night before surgery until the next day. Sleep quality characteristics, heart rate variation parameters, and apnea-hypopnea index were acquired. The diagnosis of pre-existing OSA was not considered in the current study. Results: According to apnea-hypopnea index, 28.4%, 32.2%, 26.2%, and 13.3% patients were assessed as no, mild, moderate, and severe operative OSA, respectively. Multivariate logistic regression model revealed that higher age [p < 0.001, odds ratio (OR) = 1.043] was independently and positively associated with preoperative OSA; heart rate variation parameters representing the imbalance of sympathetic/parasympathetic nervous system, such as higher low-frequency (p < 0.001, OR = 1.004), higher low-frequency/high-frequency ratio (p = 0.028, OR = 1.738), lower NN20 count divided by the total number of all NN intervals (pNN20; p < 0.001, OR = 0.950), and lower high-frequency (p < 0.001, OR = 0.998), showed independent relationships with a higher probability of preoperative OSA. Higher age (p = 0.005, OR = 1.024), higher very-low-frequency (p < 0.001, OR = 1.001), and higher low-frequency/high-frequency ratio (p = 0.003, OR = 1.655) were associated with a higher probability of moderate-to-severe preoperative OSA, but higher pNN10 (p < 0.001, OR = 0.951) was associated with a lower probability of moderate-to-severe preoperative OSA. Conclusion: Preoperative OSA is prevalent. Higher age and imbalance of sympathetic/parasympathetic nervous system are independently and positively associated with a higher occurrence of preoperative OSA. CPC screening may promote the management of preoperative OSA.

7.
Commun Biol ; 7(1): 960, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117859

ABSTRACT

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.


Subject(s)
Depressive Disorder, Major , Transcriptome , Humans , Depressive Disorder, Major/genetics , Depressive Disorder, Major/physiopathology , Female , Male , Adult , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Middle Aged , Magnetic Resonance Imaging , Gene Expression Profiling
8.
Front Med (Lausanne) ; 11: 1335084, 2024.
Article in English | MEDLINE | ID: mdl-39086954

ABSTRACT

Objective: To compare the macular area parameters and aqueous humor factors between myopia and emmetropia. Methods: Convenience sampling was used to select patients who visited the Changzhi Aier Eye Hospital's department of ophthalmology from December 2018 to December 2022 as the study participants. They were divided into three groups according to whether they were diagnosed as mild myopia myopic, highly myopic or not as follows: the mild myopia group (60 cases, 108 eyes), the high myopia group (46 cases, 78 eyes) and the healthy emmetropia group (40 cases, 65 eyes). The differences in the macular integrity (MI) assessment, optical coherence tomography and optical coherence tomography angiography parameters and aqueous humor factors were compared between the three groups. Results: AL in high myopia group was the highest, and that in emmetropia group was the lowest. The BCVA of mild myopia group was the highest. The RS in the high myopia group were significantly lowest in the three groups (26.42 ± 1.04 vs. 28.34 ± 0.76 vs. 31.92 ± 0.77) (F = 5.374, p = 0.013). The 63% BCEA, 95% BCEA and MI in the high myopia group were significantly highest (p < 0.05). The mean RPE thickness, mean CT and mean RT in the high myopia group were lowest (p < 0.05). The blood flow density were lowest in the superficial fovea, paracentral fovea and different subdivisions of the paracentral fovea in the high myopia group (p < 0.05). The VEGF concentration in the aqueous humor of the high myopia group was lowest (25.62 ± 17.43 vs. 32.45 ± 24.67 vs. 64.37 ± 21.14) (F = 9.237, p < 0.001). The MMP-2 concentration was highest (483 ± 201.48 vs. 410 ± 142.37 vs. 386 ± 154.34) (F = 5.542, p = 0.018). The VEGF concentration in the aqueous humor factor was negatively correlated with the AL in the myopia group (r = -0.438, p = 0.002), the MMP-2 concentration was positively correlated with the AL (r = 0.484, p = 0.010). Conclusion: Patients with high myopia showed decreased retinal light sensitivity, fixation stability, superficial blood flow density and retinal thickness compared with people with emmetropia. A decreased VEGF concentration and increased MMP-2 concentration in the aqueous humor factor have potential associations with the development of high myopia.

9.
BMC Infect Dis ; 24(1): 824, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143511

ABSTRACT

BACKGROUND: Sporotrichosis is a chronic granulomatous infection of the skin and subcutaneous tissue that can affect any organ through lymphatic spread. The prevalence of sporotrichosis infections is increasing and its treatment is challenging as there are no unified and standard diagnostic techniques or antifungal medications. Controlling further spread requires a rapid diagnosis. Assessment of clinical symptoms, histological analysis, serological testing, and pathogen culture are all necessary for the diagnosis of sporotrichosis. However, these procedures are unable to identify the species. The development of safe, reliable, and species-specific diagnostic techniques is essential. OBJECTIVE: To establish and evaluate a new quantitative real-time PCR assay for the rapid diagnosis of sporotrichosis and to identify relevant species. METHODS: Polymorphisms in calmodulin (CAL) gene sequences and the internal transcribed spacer (ITS) were used in a quantitative real-time PCR assay to identify S. globosa, S. schenckii, and non-target species. RESULTS: The quantitative real-time PCR assay had 100% sensitivity and specificity. The limit of detection was 6 fg/µl. Thirty-four clinical specimens were verified to be infected with S. globosa with a 100% positive detection rate. CONCLUSIONS: The quantitative PCR technique developed in this study is a quick, accurate, and targeted method of identifying S. globosa based on polymorphisms in CAL sequences and ITS. It can be used for a prompt clinical diagnosis to identify S. globosa in clinical specimens from patients with sporotrichosis.


Subject(s)
Calmodulin , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Sporothrix , Sporotrichosis , Sporotrichosis/diagnosis , Sporotrichosis/microbiology , Sporothrix/genetics , Sporothrix/isolation & purification , Humans , Real-Time Polymerase Chain Reaction/methods , Calmodulin/genetics , Asia , DNA, Fungal/genetics , Molecular Diagnostic Techniques/methods , Rapid Diagnostic Tests
10.
Sci Rep ; 14(1): 18668, 2024 08 12.
Article in English | MEDLINE | ID: mdl-39134656

ABSTRACT

Under total sleep deprivation, both inhibitory and motor control are impaired. However, how circadian rhythm sleep loss caused by irregular sleep pattern affects motor inhibition and execution in continuous actions remains unknown. This study utilized a pointing task to investigate the question over 30 days. During regular trials, participants were instructed to tap on a specified location, while in countermanding trials, they were required to countermand their current action. Additionally, there was a control group performed the same task following a normal 24-h rhythm. The results indicated that the decrease in accuracy and the increase in movement time in countermanding trials were more prominent in the shift work group. In contrast, there was no significant difference in reaction time between the two groups. Notably, the shift work group outperformed the control group in terms of movement time in regular trials and radial displacement in countermanding trials. Overall, these results show that circadian rhythm sleep loss predominantly affects inhibitory control, rather than motor control, underscoring the nuanced impacts of sleep disruption on differential aspects of cognitive and motor functions.


Subject(s)
Circadian Rhythm , Psychomotor Performance , Sleep Deprivation , Humans , Male , Circadian Rhythm/physiology , Sleep Deprivation/physiopathology , Adult , Female , Young Adult , Reaction Time/physiology
11.
Cancer Med ; 13(15): e7408, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39136200

ABSTRACT

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.


Subject(s)
Aminopyridines , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Letrozole , Postmenopause , Purines , Receptor, ErbB-2 , Receptors, Estrogen , Humans , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Aminopyridines/adverse effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Purines/administration & dosage , Purines/adverse effects , Middle Aged , Receptor, ErbB-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Receptors, Estrogen/metabolism , Letrozole/administration & dosage , Letrozole/therapeutic use , Adult , China , Aged , Receptors, Progesterone/metabolism , Premenopause , Progression-Free Survival , Goserelin/administration & dosage , Goserelin/therapeutic use , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/therapeutic use , East Asian People
12.
Redox Rep ; 29(1): 2391139, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39138590

ABSTRACT

Oxalate-induced damage to renal tubular epithelial cells (RTECs) is an essential factor in the incident kidney stone, but the specific mechanism is unclear. Recent research has pinpointed interacting areas within the endoplasmic reticulum and mitochondria, called mitochondria-associated membranes (MAMs). These studies have linked endoplasmic reticulum stress (ERS) and oxidative imbalance to kidney disease development. The sigma-1 receptor (S1R), a specific protein found in MAMs, is involved in various physiological processes, but its role in oxalate-induced kidney stone formation remains unclear. In this study, we established cellular and rat models of oxalate-induced kidney stone formation to elucidate the S1R's effects against ERS and apoptosis and its mechanism in oxalate-induced RTEC injury. We found that oxalate downregulated S1R expression in RTECs and escalated oxidative stress and ERS, culminating in increased apoptosis. The S1R agonist dimemorfan up-regulated S1R expression and mitigated ERS and oxidative stress, thereby reducing apoptosis. This protective effect was mediated through S1R inhibition of the CHOP pathway. Animal experiments demonstrated that S1R's activation attenuated oxalate-induced kidney injury and alleviated kidney stone formation. This is the first study to establish the connection between S1R and kidney stones, suggesting S1R's protective role in inhibiting ERS-mediated apoptosis to ameliorate kidney stone formation.


Subject(s)
Apoptosis , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Epithelial Cells , Kidney Tubules , Mitochondria , Nephrolithiasis , Receptors, sigma , Sigma-1 Receptor , Receptors, sigma/metabolism , Animals , Endoplasmic Reticulum Stress/drug effects , Apoptosis/drug effects , Rats , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Kidney Tubules/metabolism , Kidney Tubules/pathology , Nephrolithiasis/metabolism , Mitochondria/metabolism , Mitochondria/drug effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/drug effects , Male , Oxidative Stress/drug effects , Rats, Sprague-Dawley
13.
Article in English | MEDLINE | ID: mdl-39145810

ABSTRACT

The objective of this study is to explore the antiproliferative activity of the traditional Chinese medicine monomer vitexin on colon cancer HCT-116 cells and its underlying mechanism. The in vitro antiproliferative activity of vitexin on colon cancer HCT-116 cells was evaluated using the CCK-8 assay. Potential drug targets for colon cancer were identified through GEO chip data mining, and molecular docking using Schrödinger software was conducted. Molecular dynamics simulations were employed to deeply analyze the interaction between candidate compounds and target proteins. Flow cytometry was employed to examine the cell cycle. The impact of vitexin on the expression of CDK1/cyclinB proteins in HCT-116 cells was assessed through Western blot analysis, immunofluorescence, and CDK inhibition assay. Vitexin exhibited inhibitory effects on colon cancer HCT-116 cells, with a half inhibitory concentration (IC50) value of 203.27 ± 9.85 µmol/L. The analysis of differential gene expression in GEO and TCGA datasets, along with the GENECARD dataset of related disease genes, identified 91 disease targets, including "CDK1." Vitexin induced cell cycle arrest in the G2/M phase of HCT-116 cells. Molecular docking revealed a strong interaction between Vitexin and CDK1 (Docking score - 9.497), with molecular dynamics simulations confirming the stability of the Vitexin-CDK1 complex and comparable inhibitory effects to Flavopiridol. Vitexin can inhibit the expression of CDK1/cyclin B proteins in HCT-116 cells, with an IC50 of 58.06 ± 3.07 µmol/L. Vitexin may inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.

14.
Sci Total Environ ; 951: 175419, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39128520

ABSTRACT

Organic matter (OM) accumulation in lake sediments has doubled owing to human activities over the past 100 years, which has negatively affected the restoration of submerged vegetation and ecological security. Changes in the pollution structure of sediments caused by plant recovery and rhizosphere chemical processes under different sediment OM levels are the theoretical basis for the rational application of plant rehabilitation technology in lake management. This study explored how Vallisneria natans mediates changes in sediment N and P through rhizospheric metabolites and microbial community and function under low (4.94 %) and high (17.35 %) sediment OM levels. V. natans promoted the accumulation of NH4-N in the high-OM sediment and the transformation of Fe/Al-P to Ca-P in the low-OM sediment. By analyzing 63 rhizospheric metabolites and the sediment microbial metagenome, the metabolites lactic acid and 3-hydroxybutyric acid and the genus Anammoximicrobium were found to mediate NH4-N accumulation in the high-OM sediment. Additionally, 3-hydroxy-decanoic acid, adipic acid, and the genus Bdellovibrionaceae mediated the transformation of Fe/Al-P to Ca-P in the low-OM sediment. The growth of V. natans enriched the abundance of functional genes mediating each step from nitrate to ammonia and the genes encoding urease in the high-OM sediment, and it up-regulated three genes related to microbial phosphorus uptake in the low-OM sediment. This study revealed the necessity of controlling endogenous pollution by recovering submerged macrophytes under high- and low-OM conditions from the perspective of the transformation of inorganic nitrogen and phosphorus.

15.
Water Res ; 263: 122175, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39088878

ABSTRACT

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.


Subject(s)
Membranes, Artificial , Urine , Urine/chemistry , Waste Disposal, Fluid/methods , Wastewater/chemistry , Phosphorus , Electrochemical Techniques/methods , Nitrogen , Water Purification/methods , Fertilizers , Potassium/urine
16.
Curr Biol ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39146937

ABSTRACT

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

18.
RSC Chem Biol ; 5(9): 914-923, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39211476

ABSTRACT

N 6-methyladenosine (m6A) is an abundant modification in mammalian mRNAs and plays important regulatory roles in gene expression, primarily mediated through specific recognition by "reader" proteins. YTH family proteins are one major family of known m6A readers, which specifically recognize m6A-modified transcripts via the YTH domains. Despite the significant relevance of YTH-m6A recognition in biology and diseases, few small molecule inhibitors are available for specifically perturbing this interaction. Here we report the discovery of a new inhibitor ("N-7") for YTH-m6A RNA recognition, from the screening of a nucleoside analogue library against the YTH domain of the YTHDF1 protein. N-7 is characterized to be a pan-inhibitor in vitro against five YTH domains from human YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 proteins, with IC50 values in the range of 30-48 µM measured using a fluorescence polarization competition assay. We demonstrated that N-7 directly interacts with the YTH domain proteins via a thermal shift assay. N-7 expands the chemical structure landscape of the m6A YTH domain-containing reader inhibitors and potentiates future inhibitor development for reader functional studies and therapeutic efforts in targeting the epitranscriptome.

19.
Chemistry ; : e202402886, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39212526

ABSTRACT

The chemoselective [4+2] annulation/aromatization reactions between benzofuran-derived azadienes and N-Ts cyanamides are developed, affording a convenient method for synthesizing benzofuro[3,2-d]pyrimidin-2-amines under mild conditions. Herein, N-Ts cyanamides selectively participated in reactions absolutely via carbodiimide anion intermediates and the corresponding cyanamide anion intermediates derived products were not observed. The proposed chemoselective stepwise reaction mechanism was well supported by DFT calculations.

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