Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance.

The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Condensable and filterable particulate matter emitted from typical diesel vehicles in steady and transient driving conditions.

Condensable particulate matter (CPM) and filterable particulate matter (FPM) emitted from industrial sources have been well studied, but their emissions from vehicles have not yet been covered. This study explores the emission characteristics of CPM and FPM from typical diesel vehicles under various driving conditions. The emission factors (EFs) of CPMs under driving conditions were 5.4-10.4 times higher than those of FPMs, while CPMs EFs under transient driving conditions were about 2.5 times higher than those under steady driving conditions. CPM and FPM are mainly composed of organic matter accounting for 53.3 %-92.9 %, while the intermediate and semi-volatile organic compounds dominate the organic matter accounting for 86.3 %-98.6 %. Similar to industrial sources, alkanes are the predominant organic species emitted by diesel vehicles, comprising 42.0 %-64.0 % of the detected organic components. Inorganic CPM is primarily composed of NH4+ , representing 84.9 %-87.6 % of the total, in contrast to industrial sources where SO42- and Cl- dominate. Interestingly, the air pollution control devices installed on diesel vehicles under steady driving conditions perform better in removing organic CPM and producing higher inorganic CPM emissions than those under transient driving conditions. These findings will enhance the comprehensive understanding of particulate matter emitted from diesel vehicles and provide a scientific foundation for the development of related control technologies.

Determination and evaluation of canthaxanthin and ß-apo-8'-carotenoid ethyl ester in chicken eggs and meat in Tianjin.

Canthaxanthin and ß-apo-8'-carotenoid ethyl ester are widely used as feed additives in poultry feed for enhancing the color of poultry products. The excessive intake of the two colorants can cause health damage. According to the European Food Safety Authority (EFSA), the acceptable daily intake (ADI) of canthaxanthin and ß-apo-8'-carotenoid ethyl ester are 0.03 mg/kg·bw and 0.015 mg/kg·bw, respectively. Ultra-high-performance liquid chromatography-diode array detector (UPLC-DAD) was used to determine two colorants in chicken eggs and meat. A PRiME HLB solid-phase extraction cartridge was used to extract and clean-up the sample. BEH C18 column was used as the separation column, with water containing 0.1% formic acid and acetonitrile as the mobile phase. The limit of detection (LOD) was 0.05 mg/kg, and the limit of quantification (LOQ) was 0.1 mg/kg. The recoveries were between 90% and 104%. The daily intake of two colorants in chicken eggs and meat was evaluated based on the detection data, food consumption data and weight data of the population. The mean estimated daily intake (EDI) values of canthaxanthin through chicken eggs and meat were 1.09 µg/(kg·bw·d) and 0.013 µg/(kg·bw·d), respectively. The mean EDI value of ß-apo-8'-carotenoid ethyl ester through eggs was 0.44 µg/(kg·bw·d). The results showed that eggs were the main contributor to the daily intake of two colorants. The mean hazard quotients (HQ) values of two colorants through chicken eggs and meat was within a safe range.

Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (ß = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function.

Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Mechanism of multifunctional adaptor protein SHARPIN regulating myocardial fibrosis and how SNP mutation affect the prognosis of myocardial infarction.

Myocardial fibrosis (MF) is characterized by the excessive deposition of extracellular matrix within the heart, often following a cardiovascular insult. SHARPIN, a protein implicated in fibrosis, has emerged as a potential therapeutic target. This study aimed to elucidate the molecular mechanisms of SHARPIN in MF and to investigate the influence of its single nucleotide polymorphism (SNP), rs117299156, on myocardial infarction (MI) patients. A mouse model of Angiotensin II (AngII)-induced MF was established in SHARPIN heterozygous (SHARPIN+/-) and wild-type mice. Adult mouse cardiac fibroblasts (CFs) were isolated and subjected to adenovirus-encapsulated SHARPIN short hairpin RNA (shRNA) infection. Transcriptomic analysis was performed on CFs from SHARPIN+/- and wild-type (WT) mice, complemented by single-cell sequencing data from human cardiac tissues. Additionally, the association between the rs117299156 mutation and cardiovascular events in MI patients was assessed. Our findings indicate that SHARPIN is predominantly expressed in CFs and is upregulated in fibrotic myocardium. Partial knockdown of SHARPIN in murine hearts mitigated AngII-induced cardiac dysfunction and MF. Furthermore, reduced SHARPIN expression in CFs attenuated TGF-ß1-induced collagen synthesis, cell proliferation, and myofibroblast transformation. Notably, MI patients carrying the rs117299156_C allele exhibited a reduced incidence of stroke events compared to those without the mutation.

Emergence of Staphylococcus argenteus in pediatrics: Molecular insights from a hospital in East China.

Staphylococcus argenteus is a novel species within the Staphylococcus aureus complex and can cause serious bloodstream infections (BSIs) in humans, which have been mainly reported in adults, especially the elderly. In this study, we analyzed the molecular characterization of a strain of S. argenteus (22WJ8192) isolated from the peripheral vein blood sample of a seven-month-old female infant in Eastern China. The 22WJ8192 belonged to sequence type (ST)2250 and harbored six antibiotic-resistance genes and 53 virulence genes and was resistant to penicillin. Additionally, we conducted a comparative analysis of the molecular characteristics of S. argenteus sourced from various origins within the dataset, predominantly from the National Center for Biotechnology Information Collection (NCBI) genome database. Antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, tet(L), aph(3")-IIIa, mecA, and dfrG were more prevalent among the strains of human origin. Virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD were more prevalent among strains of human origin. The presence of antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, and aph(3")-IIIa in strain 22WJ8192 was also more common among strains of human origin in the dataset. Conversely, the antibiotic-resistance genes tet(L), mecA, and dfrG, typically found in strains of human origin, were not detected in 22WJ8192. Additionally, virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD present in 22WJ8192 exhibited a higher prevalence among strains of human origin in the dataset. In conclusion, this study emphasizes the potential of S. argenteus ST2250 to induce severe bloodstream infections in infants, shedding light on the molecular characteristics of this strain.

A cross-institutional database of operational risk external loss events in Chinese banking sector 1986-2023.

Nowadays the collection of operational risk data worldwide highly relies on human labor, leading to slow updates, data inconsistency, and limited quantity. There remains a substantial shortage of publicly accessible operational risk databases for risk analysis. This study proposes a new data collection framework by aggregating text mining methods to replace the exhausting manual collection process. The news about operational risk can be automatically collected from the web page, then its content is analyzed and the key information is extracted. Finally, the Public-Chinese Operational Loss Data (P-COLD) database for financial institutions is constructed and expanded. Each record contains 12 key information, such as occurrence time, loss amount, and business lines, offering a more thorough description of operational risk events. With 3,723 data records from 1986 to 2023, the P-COLD database has become one of the largest and most comprehensive external operational risk databases in China. We anticipate the P-COLD database will contribute to advancements in operational risk capital calculations, dependence analysis, and institutional internal controls.

Multiple-signal-joint-processing-based guard interval shortening method for a CS-NFDM system.

Aiming to further improve the spectral efficiency (SE) of a continuous spectrum modulated nonlinear frequency division multiplexing (CS-NFDM) system, we propose a novel ,to the best of our knowledge, multiple-signal-joint-processing (MSJP)-based guard interval (GI) shortening method. In this method, multiple NFDM time-domain signals are jointly processed as a whole to carry out nonlinear Fourier transform and inverse nonlinear Fourier transform (NFT-INFT) operations. These operations can fuse the multiple NFDM time-domain signals together, which is equivalent to the corresponding inverse process of a fiber transmission. Experimental results show that the normalized SE of the proposed method can reach 0.99 when approaching the limit value of 1 and obtain a 2.33 dB Q2-factor improvement compared with the pre-dispersion compensation (PDC) method under the same GI of 0.03 ns in an 80 km SSMF transmission of a 46 GHz signal bandwidth. Furthermore, in comparison with the PDC method, the proposed method can achieve 32.86% normalized SE improvement in the 1120 km SSMF transmission of 32 GHz signal bandwidth under the SD-FEC of 2.4E-2.

Rapid detection of ceftriaxone-resistant Salmonella by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry combined with the ratio of optical density.

BACKGROUND: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS). METHODS: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS. RESULTS: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10- 3]. CONCLUSIONS: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS.

The effects of foot orthoses on radiological parameters and pain in children with flexible flat feet: a systematic review and meta-analysis.

Objective: This study aimed to investigate the impact of foot orthoses on foot radiological parameters and pain in children diagnosed with flexible flatfoot. Methods: A comprehensive search was conducted across several databases, including PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO, covering publications from the inception of each database up to 8 June 2024. The study focused on randomized controlled trials investigating the use of foot orthoses for treating flexible flat feet in children. Four researchers independently reviewed the identified literature, extracted relevant data, assessed the quality of the studies, and performed statistical analyses using RevMan 5.4 software. Results: Six studies involving 297 participants were included. The methodological quality of the included literature ranged from moderate to high. Radiological parameters of the foot improved significantly in older children with flexible flat feet following foot orthotic intervention compared to controls, particularly in the lateral talar-first metatarsal angle [mean difference (MD) = -2.76, 95% confidence interval (95% CI) -4.30 to -1.21, p = 0.0005], lateral talo-heel angle (MD = -5.14, 95% CI -7.76 to -2.52, p = 0.0001) and calcaneal pitch angle (MD = 1.79, 95% CI 0.88-2.69, p = 0.0001). These differences were statistically significant. Additionally, foot orthoses significantly improved the ankle internal rotation angle and reduced foot pain in children with symptomatic flexible flatfoot (MD = -2.51, 95% CI -4.94 to -0.07, p = 0.04). Conclusion: The use of foot orthoses positively impacts the improvement of radiological parameters of the foot and reduces pain in older children with flexible flat feet. However, in younger children with flexible flat feet, the improvement from foot orthoses was not significant, likely due to challenges in radiological measurements caused by the underdevelopment of the ossification centers in the foot. Further studies are needed. Consequently, the results of this meta-analysis support the implementation of an early intervention strategy using foot orthoses for the management of symptomatic flat feet in older children. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO [CRD42023441229].

SFT-SGAT: A semi-supervised fine-tuning self-supervised graph attention network for emotion recognition and consciousness detection.

Emotional recognition is highly important in the field of brain-computer interfaces (BCIs). However, due to the individual variability in electroencephalogram (EEG) signals and the challenges in obtaining accurate emotional labels, traditional methods have shown poor performance in cross-subject emotion recognition. In this study, we propose a cross-subject EEG emotion recognition method based on a semi-supervised fine-tuning self-supervised graph attention network (SFT-SGAT). First, we model multi-channel EEG signals by constructing a graph structure that dynamically captures the spatiotemporal topological features of EEG signals. Second, we employ a self-supervised graph attention neural network to facilitate model training, mitigating the impact of signal noise on the model. Finally, a semi-supervised approach is used to fine-tune the model, enhancing its generalization ability in cross-subject classification. By combining supervised and unsupervised learning techniques, the SFT-SGAT maximizes the utility of limited labeled data in EEG emotion recognition tasks, thereby enhancing the model's performance. Experiments based on leave-one-subject-out cross-validation demonstrate that SFT-SGAT achieves state-of-the-art cross-subject emotion recognition performance on the SEED and SEED-IV datasets, with accuracies of 92.04% and 82.76%, respectively. Furthermore, experiments conducted on a self-collected dataset comprising ten healthy subjects and eight patients with disorders of consciousness (DOCs) revealed that the SFT-SGAT attains high classification performance in healthy subjects (maximum accuracy of 95.84%) and was successfully applied to DOC patients, with four patients achieving emotion recognition accuracies exceeding 60%. The experiments demonstrate the effectiveness of the proposed SFT-SGAT model in cross-subject EEG emotion recognition and its potential for assessing levels of consciousness in patients with DOC.

Associations of neutrophil-percentage-to-albumin ratio level with all-cause mortality and cardiovascular disease-cause mortality among patients with hypertension: evidence from NHANES 1999-2010.

Background: The associations of neutrophil-percentage-to-albumin ratio (NPAR) level with all-cause and cardiovascular disease (CVD)-cause mortality among patients with hypertension remain unclear. This study aims to investigate the associations of NPAR level with all-cause and CVD-cause mortality among patients with hypertension. Methods: This prospective cohort study included 8,990 patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of NPAR level with all-cause mortality and CVD-cause mortality. Restricted cubic spline analyses were used to examine the nonlinear association of NPAR level with all-cause mortality and CVD-cause mortality. Results: This cohort study included data from 8,990 participants in analysis. During 104,474 person-years of follow-up, 3,069 all-cause deaths and 1,449 CVD-cause deaths were documented. Nonlinear associations were observed for NPAR levels with risk of all-cause mortality and CVD-cause mortality among patients with hypertension. Compared with participants in T1 of NPAR, there was a significantly increased risk of all-cause mortality and CVD-cause mortality for participants in both T2 and T3 in the fully adjusted model (model 3). The corresponding HRs for all-cause mortality were 1.10 (95% CI, 0.98-1.22) and 1.63 (95% CI, 1.45-1.82). The corresponding HRs for CVD-cause mortality were 1.10 (95% CI, 0.99-1.23) and 1.63 (95% CI, 1.46-1.81). Conclusions: Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in adults with hypertension. NPAR may be clinically useful for predicting long-term health outcomes and mortality in hypertensive population.

Role of gut microbiota and metabolomics in the lipid-lowering efficacy of statins among Chinese patients with coronary heart disease and hypercholesterolemia.

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy. Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites. Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-ß-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism. Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

Luspatercept enhances hemoglobin levels in a Chinese boy with congenital sideroblastic anemia: A case report.

BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.

Do multisource data matter for NGP prediction? Evidence from the G-LSTM model.

Precisely predicting natural gas prices (NGPs) is important because it can provide the necessary decision-making basis for energy scheduling, planning and control. However, NGPs are affected by many factors and exhibit the characteristics of nonlinearity and randomness, which makes accurate predictions challenging. Therefore, in this paper, the information gain of multisource data and the global optimization ability of the gray wolf algorithm are used to build a multifactor-driven NGP hybrid forecasting model to improve the prediction performance. First, the emotional tendency and readability of news text are extracted and calculated by using VADER and textstat tools, respectively. Then the network search index is filtered and integrated by using the correlation coefficient method and the CRITIC method to form alternative variables of multisource data (news and search index). Second, the gray wolf optimization algorithm is used to find and determine the best key parameter group in long short-term memory model. Finally, the spot price of natural gas in Henry Hub from March 1, 2012 to February 28, 2022 is selected as the prediction object, and multi-scenario numerical experiments are carried out to verify the effectiveness of the proposed model. The ablation experiment results show that the information gain brought by multisource data can effectively improve the prediction effect of NGPs. Furthermore, the proposed model has the best prediction performance in different scenarios and can be regarded as a promising prediction tool.

Recruitment of FBXO22 for targeted degradation of NSD2.

Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.E1099K, resulting in growth suppression, apoptosis and reversal of drug resistance. The primary amine of UNC8732 is metabolized to an aldehyde species, which engages C326 of FBXO22 to recruit the SCFFBXO22 Cullin complex. We further demonstrate that a previously reported alkyl amine-containing degrader targeting XIAP is similarly dependent on SCFFBXO22. Overall, we present a potent NSD2 degrader for the exploration of NSD2 disease phenotypes and a new FBXO22-recruitment strategy for TPD.

Association Between Serine Concentration and Coronary Heart Disease: A Case-Control Study.

Purpose: Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients. Patients and Methods: This case-control study included 428 case-control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of >70% and controls with stenosis of <30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD. Results: Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 µg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 µg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90-0.99; P = 0.010). Patients with a serine concentration of ≥13.41 µg/mL had a lower CHD risk than those with a serine concentration of <13.41 µg/mL (odds ratio [OR] 0.57, 95% CI 0.39-0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (P interaction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87-0.98; P = 0.013) than in females. Conclusion: This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.

Functionalized Chiral Materials for Use in Chiral Sensors.

Chirality represents a fundamental attribute within living systems and is a pervasive phenomenon in the natural world. The identification and analysis of chiral materials within natural environments and biological systems hold paramount importance in clinical, chemical, and biological sciences. Within chiral analysis, there is a burgeoning focus on developing chiral sensors exhibiting exceptional selectivity, sensitivity, and stability, marking it as a forefront area of research. In the past decade (2013-2023), approximately 1990 papers concerning the application of various chiral materials in chiral sensors have been published. Biological materials and nanomaterials have important applications in the development of chiral sensors, which accounting for 26.67% and 45.24% of the material-related applications in these sensors, respectively; moreover, the development of chiral nanomaterials is closely related to the development of portable and stable chiral sensors. Natural chiral materials, utilized as selective recognition units, are combined with carriers characterized by good physical and chemical properties through functionalization to form various functional chiral materials, which improve the recognition efficiency of chiral sensors. In this article, from the perspective of biological materials, polymer materials, nanomaterials, and other functional chiral materials, the applications of chiral sensors are summarized and the research prospects of chiral sensors are discussed.

KDM6A Regulates Immune Response Genes in Multiple Myeloma.

The histone H3K27 demethylase KDM6A is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA encoding regulators of Major Histocompatibility Complex (MHC) genes. Patient data indicate that NLRC5 and CIITA, are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A and decreased gene expression. Reestablishing histone acetylation with an HDAC3 inhibitor leads to upregulation of MHC expression, offering a strategy to restore immunogenicity of KDM6A deficient tumors. Loss of Kdm6a in murine RAS-transformed fibroblasts led to increased growth in vivo associated with decreased T cell infiltration.