Machine vision-based gait scan method for identifying cognitive impairment in older adults.

Objective: Early identification of cognitive impairment in older adults could reduce the burden of age-related disabilities. Gait parameters are associated with and predictive of cognitive decline. Although a variety of sensors and machine learning analysis methods have been used in cognitive studies, a deep optimized machine vision-based method for analyzing gait to identify cognitive decline is needed. Methods: This study used a walking footage dataset of 158 adults named West China Hospital Elderly Gait, which was labelled by performance on the Short Portable Mental Status Questionnaire. We proposed a novel recognition network, Deep Optimized GaitPart (DO-GaitPart), based on silhouette and skeleton gait images. Three improvements were applied: short-term temporal template generator (STTG) in the template generation stage to decrease computational cost and minimize loss of temporal information; depth-wise spatial feature extractor (DSFE) to extract both global and local fine-grained spatial features from gait images; and multi-scale temporal aggregation (MTA), a temporal modeling method based on attention mechanism, to improve the distinguishability of gait patterns. Results: An ablation test showed that each component of DO-GaitPart was essential. DO-GaitPart excels in backpack walking scene on CASIA-B dataset, outperforming comparison methods, which were GaitSet, GaitPart, MT3D, 3D Local, TransGait, CSTL, GLN, GaitGL and SMPLGait on Gait3D dataset. The proposed machine vision gait feature identification method achieved a receiver operating characteristic/area under the curve (ROCAUC) of 0.876 (0.852-0.900) on the cognitive state classification task. Conclusion: The proposed method performed well identifying cognitive decline from the gait video datasets, making it a prospective prototype tool in cognitive assessment.

DTDHM: detection of tandem duplications based on hybrid methods using next-generation sequencing data.

Background: Tandem duplication (TD) is a common and important type of structural variation in the human genome. TDs have been shown to play an essential role in many diseases, including cancer. However, it is difficult to accurately detect TDs due to the uneven distribution of reads and the inherent complexity of next-generation sequencing (NGS) data. Methods: This article proposes a method called DTDHM (detection of tandem duplications based on hybrid methods), which utilizes NGS data to detect TDs in a single sample. DTDHM builds a pipeline that integrates read depth (RD), split read (SR), and paired-end mapping (PEM) signals. To solve the problem of uneven distribution of normal and abnormal samples, DTDHM uses the K-nearest neighbor (KNN) algorithm for multi-feature classification prediction. Then, the qualified split reads and discordant reads are extracted and analyzed to achieve accurate localization of variation sites. This article compares DTDHM with three other methods on 450 simulated datasets and five real datasets. Results: In 450 simulated data samples, DTDHM consistently maintained the highest F1-score. The average F1-score of DTDHM, SVIM, TARDIS, and TIDDIT were 80.0%, 56.2%, 43.4%, and 67.1%, respectively. The F1-score of DTDHM had a small variation range and its detection effect was the most stable and 1.2 times that of the suboptimal method. Most of the boundary biases of DTDHM fluctuated around 20 bp, and its boundary deviation detection ability was better than TARDIS and TIDDIT. In real data experiments, five real sequencing samples (NA19238, NA19239, NA19240, HG00266, and NA12891) were used to test DTDHM. The results showed that DTDHM had the highest overlap density score (ODS) and F1-score of the four methods. Conclusions: Compared with the other three methods, DTDHM achieved excellent results in terms of sensitivity, precision, F1-score, and boundary bias. These results indicate that DTDHM can be used as a reliable tool for detecting TDs from NGS data, especially in the case of low coverage depth and tumor purity samples.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Optimal Strategies for Autologous Fat Grafting in Breast Augmentation and Reconstruction: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Currently, cell-assisted lipotransfer (CAL) and platelet-rich plasma (PRP) -assisted lipotransfer have been used to overcome the low survival rate of conventional lipotransfer. However, there is still insufficient evidence to determine which technique is the best strategy for autologous fat grafting in breast cosmetic and reconstructive surgery. OBJECTIVE: The present study aimed to compare the efficacy of traditional fat transplantation, CAL, and PRP-assisted lipotransfer. METHODS: A systematic search was conducted in several databases including PUBMED, Web of Science, Cochrane, ClinicalTrials.gov, and EMBASE from January 21, 2024, to identify studies that met the inclusion criteria. Twelve studies were included after a rigorous selection process based on predefined criteria. Statistical analyses were conducted using R Ver. 4.0.5 with the netmeta and dmetar packages, employing a frequentist approach with a random-effects model. A network meta-analysis was performed to compare different fat graft procedures regarding fat survival rate and complication events. The review protocol was prospectively registered in PROSPERO (CRD42024501780). RESULTS: The results indicate that CAL and PRP-assisted lipotransfer are better than traditional fat grafts in terms of fat survival rate. And there is no significant difference in the incidence of postoperative complications between the CAL group, PRP group, and traditional group. CONCLUSION: Based on the results of network meta-analysis, it appears that both CAL and PRP-assisted lipotransfer have a higher fat survival rate for autologous fat grafting in breast augmentation and reconstruction. However, the transplantation strategy still needs to be analyzed based on actual conditions in clinical applications.

Disruption of cyclin D1 degradation leads to the development of mantle cell lymphoma.

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

Effectiveness of bone plate reduction combined with resorbable plate fixation in the treatment of large mandibular cysts.

OBJECTIVES: This study aims to observe the clinical effect of bone plate reduction in combination with a resorbable plate on large mandibular cysts. METHODS: Between October 2017 and September 2022, patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study. Intraoral approach was performed for bone plate reduction. Cone beam computed tomography (CBCT) scan was reviewed at 3, 6, and 9 months postoperatively to observe postoperative complications. Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure. RESULTS: Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated. The average thickness of the cortical bone on the labial and buccal sides was measured to be about (1.98±0.37) mm before surgery, with a mean value of (0.73±0.17) mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate. The cystic cavities were well revealed during the surgeries, which were completed successfully. Postoperatively, the wounds healed in one stage without infection. The percentages of cyst shrinkage were 20.01%, 41.76%, and 73.41% at 3, 6, and 9 months after surgery, respectively. Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software. The bone mineral densities of the adult bone were 313.78, 555.85, and 657.45 HU at the 3, 6, and 9 month time intervals, respectively. No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale. CONCLUSIONS: Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial region with the presence of cortical bone.

Wafer-Scale Fabrication of Wearable All-Carbon Nanotube Photodetector Arrays.

With electronic devices evolving toward portable and high-performance wearables, the constraints of complex and wet processing technologies become apparent. This study presents a scalable photolithography/chemical-free method for crafting wearable all-carbon nanotube (CNT) photodetector device arrays. Laser-assisted patterning and dry deposition techniques directly assemble gas-phase CNTs into flexible devices without any lithography or lift-off processes. The resulting wafer-scale all-CNT photodetector arrays showcase excellent uniformity, wearability, environmental stability, and notable broadband photoresponse, boasting a high responsivity of 44 AW-1 and a simultaneous detectivity of 1.9 × 109 Jones. This research provides an efficient, versatile, and scalable strategy for manufacturing wearable all-CNT device arrays, allowing widespread adoption in wearable optoelectronics and multifunctional sensors.

Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis. METHODS: The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens. RESULTS: A total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs. CONCLUSION: In summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.

Efficacy of Xuebijing injection for the treatment of acute lung injury: A meta-analysis of randomized controlled trials.

Background: Management guidelines for acute lung injury (ALI) are extremely limited. Xuebijing, a traditional Chinese medicine, exerts therapeutic effects in patients with ALI; however, supportive evidence is currently insufficient. Material and methods: A systematic literature search of seven electronic databases for randomised controlled trials assessing the efficacy of Xuebijing injections in patients with ALI, published from inception to March 31, 2024, was performed. The Risk of Bias assessment tool recommended by The Cochrane Collaboration was used for quality evaluation. Review Manager version 5.3 (R Foundation for Statistical Computing, Vienna, Austria) was used for analysis. Dichotomous variables are expressed as relative risk (RR) and continuous variables as standardised mean difference (SMD). Heterogeneity was assessed using the I 2 statistic and a funnel plot was used to visually assess publication bias. Results: Sixteen studies comprising 1327 patients were included. Xuebijing injection improved oxygenation index (SMD 1.08 [95 % confidence interval (CI) 0.79-1.38]), reduced the incidence of acute respiratory distress syndrome (RR 0.56 [95 % CI 0.42-0.74) and all-cause mortality (RR 0.48 [95 % CI 0.34-0.67]), and decreased serum tumor necrosis factor-alpha (SMD -1.33 [95 % CI -1.50 to -1.17]) and interleukin-6 levels (SMD -1.35 [95 % CI -1.52 to -1.17]). The funnel plot indicated no publication bias. Conclusion: Xuebijing injection may be an effective treatment for ALI. However, this needs to be further confirmed in well-designed, large-sample, randomised controlled trials.

Investigating the impact of ultrasound-assisted treatment on the crafting of mulberry leaf protein and whey isolate complex: A comprehensive analysis of structure and functionality.

Mulberry leaf protein (MLP) is a nutrient-rich protein, but its applicability is limited because of its poor solubility. To address this issue, this study combines MLP with whey protein isolates (WPI), known for the high nutritional value, and subsequently forms composite protein nanoparticles using the ultrasound-assisted pH shifting method. Microscopic observation and SDS-PAGE confirmed the binding between these two proteins. Fluorescence spectra and Fourier Transform infrared spectroscopy (FTIR) analysis supported the involvement of electrostatic interactions, hydrophobic attractions, and hydrogen bonding in the formation of stable complex nanoparticles. The interactions between the proteins became stronger after ultrasound-assisted pH-shifting treatment. Solubility, emulsification capacity, foaming, and antioxidant activity, among other indicators, demonstrate that the prepared composite nanoparticles exhibit favorable functional properties. The study successfully illustrates the creation of protein-based complex nanoparticles through the ultrasound-assisted pH shifting method, with potential applications in the delivery of bioactive compounds.

Hidden blood loss and its risk factors after hip reconstruction in children.

OBJECTIVE: There were few reports in the literature regarding hidden blood loss following surgery for developmental dysplasia of the hip in children. This study aimed to evaluate the volume of hidden blood loss and its risk factors among children undergoing hip reconstruction for developmental dysplasia of the hip. METHODS: A retrospective analysis of clinical data from 42 patients (58 hips), who underwent Pemberton and femoral osteotomies between March 2020 and March 2023, was conducted. Serial complete blood count assays were conducted on the day of admission and four days post-surgery. Preoperative and postoperative hematocrit levels were documented to calculate hidden blood loss utilizing the Gross formula. Pearson and Spearman correlation analyses, along with multivariable linear regression, were employed to ascertain associations between patient characteristics and hidden blood loss. RESULTS: The mean hidden blood loss was recorded as 283.06 ± 271.05 mL, constituting 70.22% of the total blood loss. Multiple linear regression analysis identified weight and surgical duration as independent risk factors contributing to hidden blood loss. CONCLUSIONS: A relevant amount of postoperative hidden blood loss occurs after Pemberton osteotomy and femoral osteotomy for developmental dysplasia of the hip. Surgeons should be aware that patients who require blood transfusions and have longer surgical durations are at a higher risk of developing more hidden blood loss. Therefore, attention should be given to hidden blood loss to ensure patient safety during the perioperative period for those undergoing Pemberton and femoral osteotomies. LEVEL OF EVIDENCE: IV.

Acral persistent papular mucinosis: a rare child case report and literature review.

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper. Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far. Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM.

Assessing the current situation and the influencing factors affecting perceived stigma among older patients after leukemia diagnosis.

BACKGROUND: Psychological problems are becoming increasingly prominent among older patients with leukemia, with patients potentially facing stigmatization after diagnosis. However, there is limited research on the stigma experienced by these patients and the factors that may contribute to it. AIM: To investigate the stigma faced by older patients after being diagnosed with leukemia and to analyze the potential influencing factors. METHODS: A retrospective analysis was conducted using clinical data obtained from questionnaire surveys, interviews, and the medical records of older patients with leukemia admitted to the Hengyang Medical School from June 2020 to June 2023. The data obtained included participants' basic demographic information, medical history, leukemia type, family history of leukemia, average monthly family income, pension, and tendency to conceal illness. The Chinese versions of the Social Impact Scale (SIS), Perceived Social Support Scale (PSSS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess indicators related to stigma, social support, and mental health status. We used Pearson's correlation coefficient to analyze the strength and direction of the relationship between the scores of each scale, and regression analysis to explore the factors related to the stigma of older patients with leukemia after diagnosis. RESULTS: Data from 120 patients with leukemia aged 65-80 years were analyzed. The total score on the SIS and PSSS was 43.60 ± 4.07 and 37.06 ± 2.87, respectively. The SAS score was 58.35 ± 8.32 and the SDS score was 60.58 ± 5.97. The stigma experienced by older leukemia patients was negatively correlated with social support (r = -0.691, P < 0.05) and positively correlated with anxiety and depression (r = 0.506, 0.382, P < 0.05). Age, education level, smoking status, average monthly family income, pension, and tendency to conceal illness were significantly associated with the participants' level of stigma (P < 0.05). Age, smoking status, social support, anxiety, and depression were predictive factors of stigmatization among older leukemia patients after diagnosis (all P < 0.05), with a coefficient of determination (R2) of 0.644 and an adjusted R2 of 0.607. CONCLUSION: Older patients commonly experience stigmatization after being diagnosed with leukemia. Factors such as age, smoking status, social support, and psychological well-being may influence older patients' reported experience of stigma.

CircDUSP22 Attenuates the Ferroptosis of Prostate Cancer Cells via miR-18a-5p/SLC7A11/GPX4 Signaling.

BACKGROUND: According to current worldwide cancer data, Prostate Cancer (PC) ranks as the second most common type of cancer and is the fifth leading cause of cancer-related mortality among men worldwide. PC in China has the 10th highest number of new cases and the 13th highest fatality rate, both of which show an ongoing annual increase. One of the significant challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful in controlling the progression of prostate cancer, almost all tumors that respond to hormones eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24 months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic approaches. Therefore, understanding the fundamental mechanisms of prostate cancer development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers are crucial objectives. METHODS: CircRNA expression in plasma was assessed in 4 samples obtained from patients with Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical analysis of the expression of circDUSP22 and clinicopathological features was conducted. The investigation of target genes was conducted using luciferase reporter assays and bioinformatics analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member 11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction (qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation (RIP) and dual-luciferase reporter assays were used to examine the connections among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and ROS were also examined. RESULTS: In both plasma samples and PCa cell lines, there was a substantial elevation of circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro. The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of circDUSP22's competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing of circDUSP22. CONCLUSION: The circDUSP22 has been found to have a substantial effect on the development of ferroptosis in PC. It has been observed to influence the formation and evolution of this disorder by affecting the miR-18a-5p/SLC7A11 signaling pathway.

The Simultaneous Bilateral Surgical Procedure for Bilateral Primary Lung Cancer.

Objective: At present, the incidence of synchronous multiple primary lung cancer (SMPLC) is increasing, and the treatment is still a challenge. This study aims to investigate the appropriate surgical procedure for treating bilateral primary lung cancer simultaneously. Methods: A retrospective analysis was conducted on clinical data from 32 patients who underwent simultaneous bilateral lung cancer surgery in our team. This data included patient characteristics, pulmonary function indicators, surgical procedures, operation duration, chest tube removal time, postoperative hospital stay, and postoperative complications. Results: Out of the 32 patients, 15 were male, and 17 were female, with an average age of 56.4 ± 8.8 years. The average maximum diameter of the main and minor tumors was 1.8 ± 1.0 cm and 1.0 ± .5 cm, respectively. All surgeries were performed thoracoscopically through intercostal approach. The procedure for the minor tumor was performed first, followed by the main tumor operation after turning over. One case was converted to thoracotomy during the main tumor operation because of bleeding. Postoperative complications occurred in one patient. No instances of respiratory insufficiency or failure were observed after the operation, and there were no perioperative deaths or readmissions within 90 days. Conclusion: Simultaneous bilateral thoracoscopic surgery is deemed a secure and feasible option for eligible patients with bilateral primary lung cancer, and it is advisable to commence the operation on the minor tumor first.

Mechanism of discoloration of Antarctic krill oil upon storage: A study based on model systems.

The reddish-orange color of Antarctic krill oil fades during storage, and the mechanism remains unclear. Model systems containing different combinations of astaxanthin (ASTA), phosphatidylethanolamine (PE), and tocopherol were subjected to accelerated storage. Among all groups containing ASTA, only the ones with added PE showed significant fading. Meanwhile, the specific UV-visible absorption (A470 and A495) showed a similar trend. Peroxide value and thiobarbituric acid reactive substances increased during storage, while ASTA and PE contents decreased. Correlation analysis suggested that oxidized PE promoted fading by accelerating the transformation of ASTA. PE content exceeded the critical micelle concentration (1µg/g) indicating the formation of reverse micelles. Molecular docking analysis indicated that PE also interacted with ASTA in an anchor-like manner. Therefore, it is speculated that amphiphilic ASTA is more readily distributed at the oil-water interface of reverse micelles and captured by oxidized PE, which facilitates oxidation transfer, leading to ASTA oxidation and color fading.

Dysregulation of hepatic one-carbon metabolism in classical homocystinuria: Implications of redox-sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment.

Cystathionine beta-synthase-deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10-fold increase in hepatic levels of 5-methyl -THF and a 30-fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF-generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU-mediated induction of the 20-hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one-carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.

Optimize individualized energy delivery for septic patients using predictive deep learning models.

BACKGROUND AND OBJECTIVES: We aim to establish deep learning models to optimize the individualized energy delivery for septic patients. METHODS AND STUDY DESIGN: We conducted a study of adult septic patients in ICU, collecting 47 indicators for 14 days. We filtered out nutrition-related features and divided the data into datasets according to the three metabolic phases proposed by ESPEN: acute early, acute late, and rehabilitation. We then established optimal energy target models for each phase using deep learning and conducted external validation. RESULTS: A total of 179 patients in training dataset and 98 patients in external validation dataset were included in this study, and total data size was 3115 elements. The age, weight and BMI of the patients were 63.05 (95%CI 60.42-65.68), 61.31(95%CI 59.62-63.00) and 22.70 (95%CI 22.21-23.19), respectively. And 26.0% (72) of the patients were female. The models indicated that the optimal energy targets in the three phases were 900kcal/d, 2300kcal/d, and 2000kcal/d, respectively. Excessive energy intake increased mortality rapidly in the early period of the acute phase. Insufficient energy in the late period of the acute phase significantly raised the mortality as well. For the rehabilitation phase, too much or too little energy delivery were both associated with elevated death risk. CONCLUSIONS: Our study established time-series prediction models for septic patients to optimize energy delivery in the ICU. We recommended permissive underfeeding only in the early acute phase. Later, increased energy intake may improve survival and settle energy debts caused by underfeeding.

Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Autocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma.

Lymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was related to LNM. s-MDK combined with serum-squamous cell carcinoma antigen(s-SCCA) improved the diagnostic accuracy of CSCC LNM. These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.