Mechanical guidance to self-organization and pattern formation of stem cells.

The self-organization of stem cells (SCs) constitutes the fundamental basis of the development of biological organs and structures. SC-driven patterns are essential for tissue engineering, yet unguided SCs tend to form chaotic patterns, impeding progress in biomedical engineering. Here, we show that simple geometric constraints can be used as an effective mechanical modulation approach that promotes the development of controlled self-organization and pattern formation of SCs. Using the applied SC guidance with geometric constraints, we experimentally uncover a remarkable deviation in cell aggregate orientation from a random direction to a specific orientation. Subsequently, we propose a dynamic mechanical framework, including cells, the extracellular matrix (ECM), and the culture environment, to characterize the specific orientation deflection of guided cell aggregates relative to initial geometric constraints, which agrees well with experimental observation. Based on this framework, we further devise various theoretical strategies to realize complex biological patterns, such as radial and concentric structures. Our study highlights the key role of mechanical factors and geometric constraints in governing SCs' self-organization. These findings yield critical insights into the regulation of SC-driven pattern formation and hold great promise for advancements in tissue engineering and bioactive material design for regenerative application.

Inorganic-organic hybrid Cu-dipyridyl semiconducting polymers based on the redox-active cluster [SFe3(CO)9]2-: filling the gap in iron carbonyl chalcogenide polymers.

The construction of sulfur-incorporated cluster-based coordination polymers was limited and underexplored due to the lack of efficient synthetic routes. Herein, we report facile mechanochemical ways toward a new series of SFe3(CO)9-based dipyridyl-Cu polymers by three-component reactions of [Et4N]2[SFe3(CO)9] ([Et4N]2[1]) and [Cu(MeCN)4][BF4] with conjugated or conjugation-interrupted dipyridyl ligands, 1,2-bis(4-pyridyl)ethylene (bpee), 1,2-bis(4-pyridyl)ethane (bpea), 4,4'-dipyridyl (dpy), or 1,3-bis(4-pyridyl)propane (bpp), respectively. X-ray analysis showed that bpee-containing 2D polymers demonstrated unique SFe3(CO)9 cluster-armed and cluster-one-armed coordination modes via the hypervalent µ5-S atom. These S-Fe-Cu polymers could undergo flexible structural transformations with the change of cluster bonding modes by grinding with stoichiometric amounts of dipyridyls or 1/[Cu(MeCN)4]+. They exhibited semiconducting behaviors with low energy gaps of 1.55-1.79 eV and good electrical conductivities of 3.26 × 10-8-1.48 × 10-6 S cm-1, tuned by the SFe3(CO)9 cluster bonding modes accompanied by secondary interactions in the solid state. The electron transport efficiency of these polymers was further elucidated by solid-state packing, X-ray photoelectron spectroscopy (XPS), X-ray absorption near-edge spectroscopy (XANES), density of states (DOS), and crystal orbital Hamilton population (COHP) analysis. Finally, the solid-state electrochemistry of these polymers demonstrated redox-active behaviors with cathodically-shifted patterns compared to that of [Et4N]2[1], showing that their efficient electron communication was effectively enhanced by introducing 1 and dipyridyls as hybrid ligands into Cu+-containing networks.

Low blood flow ratio is associated with hemorrhagic transformation secondary to mechanical thrombectomy in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: A significant decrease of cerebral blood flow (CBF) is a risk factor for hemorrhagic transformation (HT) in acute ischemic stroke (AIS). This study aimed to ascertain whether the ratio of different CBF thresholds derived from computed tomography perfusion (CTP) is an independent risk factor for HT after mechanical thrombectomy (MT). METHODS: A retrospective single center cohort study was conducted on patients with AIS undergoing MT at the First Affiliated Hospital of Wenzhou Medical University from August 2018 to December 2023. The perfusion parameters before thrombectomy were obtained according to CTP automatic processing software. The low blood flow ratio (LFR) was defined as the ratio of brain volume with relative CBF <20 % over volume with relative CBF <30 %. HT was evaluated on the follow-up CT images. Binary logistic regression was used to analyze the correlation between parameters that differ between the two groups with regards to HT occurrence. The predictive efficacy was assessed utilizing the receiver operating characteristic curve. RESULTS: In total, 243 patients met the inclusion criteria. During the follow-up, 46.5 % of the patients (113/243) developed HT. Compared with the Non-HT group, the HT group had a higher LFR (0.47 (0.34-0.65) vs. 0.32 (0.07-0.56); P < 0.001). According to the binary logistic regression analysis, the LFR (aOR: 6.737; 95 % CI: 1.994-22.758; P = 0.002), Hypertension history (aOR: 2.231; 95 % CI: 1.201-4.142; P = 0.011), plasma FIB levels before MT (aOR: 0.641; 95 % CI: 0.456-0.902; P = 0.011), and the mismatch ratio (aOR: 0.990; 95 % CI: 0.980-0.999; P = 0.030) were independently associated with HT secondary to MT. The area under the curve of the regression model for predicting HT was 0.741. CONCLUSION: LFR, a ratio quantified via CTP, demonstrates potential as an independent risk factor of HT secondary to MT.

Theoretical Analysis of Selectivity Differences in Ketoreductases toward Aldehyde and Ketone Carbonyl Groups.

Lactobacillus kefir alcohol dehydrogenase (LkADH) and ketoreductase from Chryseobacterium sp. CA49 (ChKRED12) exhibit different chemoselectivity and stereoselectivity toward a substrate with both keto and aldehyde carbonyl groups. LkADH selectively reduces the keto carbonyl group while retaining the aldehyde carbonyl group, producing optically pure R-alcohols. In contrast, ChKRED12 selectively reduces the aldehyde group and exhibits low reactivity toward ketone carbonyls. This study investigated the structural basis for these differences and the role of specific residues in the active site. Molecular dynamics (MD) simulations and quantum chemical calculations were used to investigate the interactions between the substrate and the enzymes and the essential cause of this phenomenon. The present study has revealed that LkADH and ChKRED12 exhibit significant differences in the structure of their respective active pockets, which is a crucial determinant of their distinct chemoselectivity toward the same substrate. Moreover, residues N89, N113, and E144 within LkADH as well as Q151 and D190 within ChKRED12 have been identified as key contributors to substrate stabilization within the active pocket through electrostatic interactions and van der Waals forces, followed by hydride transfer utilizing the coenzyme NADPH. Furthermore, the enantioselectivity mechanism of LkADH has been elucidated using quantum chemical methods. Overall, these findings not only provide fundamental insights into the underlying reasons for the observed differences in selectivity but also offer a detailed mechanistic understanding of the catalytic reaction.

Comparative Study of Heavy Metal Blood Serum Level Between Organic and Conventional Farmers in Eastern Taiwan.

Numerous studies have indicated that organic fertilizers (OFer) might contain heavy metals (HMs) that present health risks to organic farmers (OFar). This study compared the concentrations of six HMs (Zn, Ni, Cd, Cu, Pb, Cr) in the blood of two distinct groups of farmers: 30 OFar from a designated organic area in eastern Taiwan, and 74 conventional farmers (CFar) from neighboring non-organic designated regions. The findings revealed that the OFar exhibited higher levels of Zn (1202.70 ± 188.74 µg/L), Cr (0.20 ± 0.09 µg/L), and Ni (2.14 ± 1.48 µg/L) in their blood compared to the CFar (988.40 ± 163.16 µg/L, 0.18 ± 0.15 µg/L, and 0.77 ± 1.23 µg/L), respectively. The disparities in Zn, Cr, and Ni levels were measured at 214.3 µg/L, 0.02 µg/L, and 1.37 µg/L, respectively. Furthermore, among the OFar, those who utilized green manures (GM) displayed significantly elevated blood levels of Zn (1279.93 ± 156.30 µg/L), Cr (0.24 ± 0.11 µg/L), and Ni (1.94 ± 1.38 µg/L) compared to individuals who exclusively employed chemical fertilizers (CFer) (975.42 ± 165.35 µg/L, 0.19 ± 0.16 µg/L, and 0.74 ± 1.20 µg/L), respectively. The differences in Zn, Cr, and Ni levels were measured at 304.51 µg/L, 0.05 µg/L, and 1.20 µg/L, respectively. As a result, OFar should be careful in choosing OFer and avoid those that may have heavy metal contamination.

Alter codon bias of the P. pastoris genome to overcome a bottleneck in codon optimization strategy development and improve protein expression.

Apart from its role in translation, codon bias is also an important mechanism to regulate mRNA levels. The traditional frequency-based codon optimization strategy is rather efficient in organisms such as N. crassa, but much less in yeast P. pastoris which is a popular host for heterologous protein expression. This is because that unlike N. crassa, the preferred codons of P. pastoris are actually AU-rich and hence codon optimization for extremely low GC content comes with issues of pre-mature transcriptional termination or low RNA stability in spite of translational advantages. To overcome this bottleneck, we focused on three reporter genes in P. pastoris first and confirmed the great advantage of GC-prone codon optimization on mRNA levels. Then we altered the codon bias profile of P. pastoris by introducing additional rare tRNA gene copies. Prior to that we constructed IPTG-regulated tRNA species to enable chassis cells to switch between different codon bias status. As demonstrated again with reporter genes, protein yield of luc and 0788 was successfully increased by 4-5 folds in chassis cells. In summary, here we provide an alternative codon optimization strategy for genes with unsatisfactory performance under traditional codon frequency-based optimization.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Unravelling the mechanisms of underweight in Parkinson's disease by investigating into the role of gut microbiome.

Approximately half of patients with Parkinson's disease (PD) suffer from unintentional weight loss and are underweight, complicating the clinical course of PD patients. Gut microbiota alteration has been proven to be associated with PD, and recent studies have shown that gut microbiota could lead to muscle wasting, implying a possible role of gut microbiota in underweight PD. In this study, we aimed to (1) investigate the mechanism underlying underweight in PD patients with respect to gut microbiota and (2) estimate the extent to which gut microbiota may mediate PD-related underweight through mediation analysis. The data were adapted from Hill-Burns et al., in which 330 participants (199 PD, 131 controls) were enrolled in the study. Fecal samples were collected from participants for microbiome analysis. 16S rRNA gene sequence data were processed using DADA2. Mediation analysis was performed to quantify the effect of intestinal microbial alteration on the causal effect of PD on underweight and to identify the key bacteria that significantly mediated PD-related underweight. The results showed that the PD group had significantly more underweight patients (body mass index (BMI) < 18.5) after controlling for age and sex. Ten genera and four species were significantly different in relative abundance between the underweight and non-underweight individuals in the PD group. Mediation analysis showed that 42.29% and 37.91% of the effect of PD on underweight was mediated through intestinal microbial alterations at the genus and species levels, respectively. Five genera (Agathobacter, Eisenbergiella, Fusicatenibacter, Roseburia, Ruminococcaceae_UCG_013) showed significant mediation effects. In conclusion, we found that up to 42.29% of underweight PD cases are mediated by gut microbiota, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria, which indicates that the pro-inflammatory state, disturbance of metabolism, and interference of appetite regulation may be involved in the mechanism of underweight PD.

sTREM2 in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

BACKGROUND: Previous studies have shown that TREM2 plays a protective role in acute lung injury (ALI). This prospective study aimed to investigate the role of sTREM2 as a forecasting factor for ALI in infants after pediatric cardiac surgery undergoing cardiopulmonary bypass (CPB). METHODS: Seventy-five consecutive patients younger than 1 year who underwent cardiac surgery were enrolled in this study. Sixty-one fulfilled the inclusion criteria and had been divided into ALI and non-ALI groups. Children's demographic characteristics and clinical data were collected. Perioperative sTREM2 levels were analyzed at five timepoints. RESULTS: In this study, children in the ALI group were younger, lighter, with higher RACHS-1 scores and underwent significantly longer CPB time. Post-CPB ALI had an impact on clinical outcomes, which contributed to a longer duration of mechanical ventilation, ICU and hospital stay than non-ALI group. Significant differences were manifested off-CPB, 1 h/6 h after CPB, and day 1 after surgery between the two groups. Binary logistic models revealed that off-CPB sTREM2 was significantly associated with the incidence of post-CPB ALI after adjustment. ROC analysis showed that the AUC of off-CPB sTREM2 level was 0.791, and the optimal cutoff value was 788.6 pg/ml. CONCLUSIONS: The off-CPB sTREM2 level was an independent prognostic factor for post-CPB ALI in infants. IMPACT: Plasma sTREM2 works together with downstream TREM2 to regulate inflammation response by binding the receptor to other cells. Previous studies have shown that TREM2 plays a protective role in ischemia-reperfusion and has anti-inflammatory effects on acute lung injury (ALI). This study analyzed the risk factors of post-cardiopulmonary bypass (CPB) ALI. We found that weight and off-CPB sTREM2 level were independent prognostic factors for post-CPB ALI. Plasma sTREM2 may serve as an early biomarker in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Acute Phase Blood Glucose Levels and Functional Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

Objective: Post-stroke hyperglycemia as a common phenomenon is associated with unfavorable outcomes. Focusing on admission hyperglycemia, other markers of dysglycemia were overlooked. This study aimed to explore the contribution of acute phase blood glucose levels in combination with other radiological signs to the prognostication of functional outcomes in patients with spontaneous intracerebral hemorrhage (sICH). Methods: Consecutive patients with sICH with at least five random plasma glucose measurements and complete radiological data during hospitalization were included. We calculated the average, maximum, minimum, standard deviation, and coefficient of variation of blood glucose levels for each patient. Radiological data, including island, black hole, blend, and satellite signs were collected. Functional outcomes were evaluated using the Barthel index. Unfavorable outcomes were defined as a Barthel index score ≤ 60. Univariate and multivariate analyses were performed to identify independent predictors of unfavorable outcomes. Results: Two hundred and thirty-eight patients (mean age 58.5, 163 men and 75 women) were included, and 71 had a history of diabetes. Unfavorable outcomes occurred in 107 patients (45.0%) at 3 months. Multivariate logistic regression analysis demonstrated that maximum blood glucose levels (odds ratio, 1.256; 95% confidence interval, 1.124‒1.404; p < 0.001) and island sign (odds ratio, 2.701; 95% confidence interval, 1.322‒5.521; p = 0.006) were independent predictors of unfavorable outcomes in the nondiabetic group. Meanwhile, patients without diabetes who experienced hematoma expansion had higher average (p = 0.036) and maximum blood glucose levels (p = 0.014). Interpretation: Maximum blood glucose levels and island sign were independently associated with unfavorable outcomes in patients without diabetes, whereas no glycemic variability indices were associated with unfavorable outcomes. Glucose levels influenced hematoma expansion and functional outcomes, particularly in patients without diabetes with sICH. Thus, clinical management of blood glucose levels should be strengthened for patients with sICH with or without a history of diabetes.

Recommended Values for the Hydrophobicity and Mechanical Properties of Coating Materials Usable for Preparing Controlled-Release Fertilizers.

The hydrophobicity and mechanical properties of coating materials and the nitrogen (N) release rates of 11 kinds of controlled-release fertilizers (CRFs) were determined in this study. The results show that the N release periods of the CRFs had negative correlations with the water absorption (WA) of the coating materials (y = 166.06x-1.24, r = 0.986), while they were positively correlated with the water contact angle (WCA) and elongation at break (EB) (y = 37.28x0.18, r = 0.701; y = -19.42 + 2.57x, r = 0.737). According to the fitted functional equation, CRFs that could fulfil the N release period of 30 days had a coating material WA < 2.4%, WCA > 68.8°, and EB > 57.7%. The recommended values for a CRF that can fulfil the N release period of 30 days are WA < 3.0%, WCA > 60.0°, and EB > 30.0% in the coating materials. CRFs with different nutrient release periods can be designed according to the recommended values to meet the needs of different crops. Furthermore, our experiments have illustrated that the N release period target of 30 days can be reached for modified sulfur-coated fertilizers (MSCFs) by improving their mechanical properties.

Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.

BACKGROUND: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. METHODS: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. RESULTS: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. CONCLUSIONS: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

Spatially Resolved Organic Whispering-Gallery-Mode Hetero-Microrings for High-Security Photonic Barcodes.

Whispering-gallery-mode (WGM) microcavities featuring distinguishable sharp peaks in a broadband exhibit enormous advantages in the field of miniaturized photonic barcodes. However, such kind of barcodes developed hitherto are primarily based on microcavities wherein multiple gain medias were blended into a single matrix, thus resulting in the limited and indistinguishable coding elements. Here, a surface tension assisted heterogeneous assembly strategy is proposed to construct the spatially resolved WGM hetero-microrings with multiple spatial colors along its circular direction. Through precisely regulating the charge-transfer (CT) strength, full-color microrings covering the entire visible range were effectively acquired, which exhibit a series of sharp and recognizable peaks and allow for the effective construction of high-quality photonic barcodes. Notably, the spatially resolved WGM hetero-microrings with multiple coding elements were finally acquired through heterogeneous nucleation and growth controlled by the directional diffusion between the hetero-emulsion droplets, thus remarkably promoting the security strength and coding capacity of the barcodes. The results would be useful to fabricate new types of organic hierarchical hybrid WGM heterostructures for optical information recording and security labels.

Machine learning prediction model for the rupture status of middle cerebral artery aneurysm in patients with hypertension: a Chinese multicenter study.

Background: Hypertension is a common comorbidity in patients with unruptured intracranial aneurysms and is closely associated with the rupture of aneurysms. However, only a few studies have focused on the rupture risk of aneurysms comorbid with hypertension. This retrospective study aimed to construct prediction models for the rupture of middle cerebral artery (MCA) aneurysm associated with hypertension using machine learning (ML) algorithms, and the constructed models were externally validated with multicenter datasets. Methods: We included 322 MCA aneurysm patients comorbid with hypertension who were being treated in four hospitals. All participants underwent computed tomography angiography (CTA), and aneurysm morphological features were measured. Clinical characteristics included sex, age, smoking, and hypertension history. Based on the clinical and morphological characteristics, the training datasets (n=277) were used to fit the ML algorithms to construct prediction models, which were externally validated with the testing datasets (n=45). The prediction performances of the models were assessed by receiver operating characteristic (ROC) curves. Results: The areas under the ROC curve (AUCs) of the k-nearest-neighbor (KNN), neural network (NNet), support vector machine (SVM) and logistic regression (LR) models in the training datasets were 0.83 [95% confidence interval (CI): 0.78-0.88], 0.87 (95% CI: 0.82-0.92), 0.91 (95% CI: 0.88-0.95), and 0.83 (95% CI: 0.77-0.88), respectively, and in the testing datasets were 0.74 (95% CI: 0.59-0.89), 0.82 (95% CI: 0.69-0.94), 0.73 (95% CI: 0.58-0.88), and 0.76 (95% CI: 0.61-0.90), respectively. The aspect ratio (AR) was ranked as the most important variable in the ML models except for NNet. Further analysis showed that the AR had good diagnostic performance, with AUC values of 0.75 in the training datasets and 0.77 in the testing datasets. Conclusions: The ML models performed reasonably accurately in predicting MCA aneurysm rupture comorbid with hypertension. AR was demonstrated as the leading predictor for the rupture of MCA aneurysm with hypertension.

Serum soluble triggering receptor levels expressed on myeloid cells2 identify early acute kidney injury in infants and young children after pediatric cardiopulmonary bypass.

Background: Acute kidney injury (AKI) is a potential complication after cardiopulmonary bypass (CPB) of pediatric cardiac surgery and contributes to a certain amount of perioperative mortality. Serum soluble triggering receptor expressed on myeloid cells2 (sTREM2) is an inflammation-associated cytokine in circulation. Alterations of sTREM2 level have been reported in Alzheimer's disease, sepsis, and some other pathologic conditions. This study aimed to investigate the role of sTREM2 as a forecasting factor for AKI in infants and young children and other factors associated with early renal injury after pediatric CPB. Methods: A prospective cohort study with consecutive infants and young children ≤ 3 years old undergoing CPB from September 2021 to August 2022 was conducted in an affiliated university children's hospital. These patients were divided into an AKI group (n = 10) and a non-AKI group (n = 60). Children's characteristics and clinical data were measured. Perioperative sTREM2 levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Results: In children developing AKI, the sTREM2 levels significantly decreased at the beginning of CPB compared to the non-AKI group. Based on binary logistic regression analysis and multivariable regression analysis, risk-adjusted classification for congenital heart surgery (RACHS-1), operation time, and the s-TREM2 level at the beginning of CPB (AUC = 0.839, p = 0.001, optimal cut-off value: 716.0 pg/ml) had predictive value for post-CPB AKI. When combining the sTREM2 level at the beginning of CPB and other indicators together, the area under the ROC curve enlarged. Conclusions: Operation time, RACHS-1 score, and sTREM2 level at the beginning of CPB were independent prognosis factors of post-CPB AKI in infants and young children ≤ 3 years old. Decreased sTREM2 identified post-CPB AKI, and ultimately hampered the outcomes. Our findings indicated that sTREM2 may be a protective factor for AKI after CPB in infants and young children ≤ 3 years old.

Rational Design of pH-Independent and High-Fidelity Near-Infrared Tunable Fluorescent Probes for Tracking Leucine Aminopeptidase In Vivo.

Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.

A marine lipopeptides-producing Bacillus amyloliquefaciens HY2-1 with a broad-spectrum antifungal and antibacterial activity and its fermentation kinetics study.

The antagonistic Bacillus amyloliquefaciens HY2-1 was a marine microbiology that was isolated previously from the seabed silt of Beibu Gulf in China by dual culture with Penicillium digitatum. As a continuous study, the present work focused on evaluating the antimicrobial activity, identifying the produced active components, and revealing the fermentation characteristics of B. amyloliquefaciens HY2-1, respectively. It was found that B. amyloliquefaciens HY2-1 exhibited a broad-spectrum antimicrobial activity against the tested seven phytopathogenic fungi and five pathogenic bacteria by producing Bacillus lipopeptides such as fengycin A (C14 to C19 homologues) and surfactin (C14 and C15 homologues). Morphological observation of P. digitatum under light microscope, scanning electron microscopy, transmission electron microscopy, and fluorescence microscope inferred that B. amyloliquefaciens exerted the antagonistic activity by damaging the fungal cell membrane, thus inhibiting the mycelium growth and sporification of phytopathogenic fungi. As a marine microbiology, our results showed that B. amyloliquefaciens could survive and metabolize even at the culture condition with 110 g/L of NaCl concentration, and the produced antimicrobial compounds exhibited excellent thermostability and acid-alkali tolerance. The dynamic models were further constructed to theoretically analyze the fermentation process of B. amyloliquefaciens HY2-1, suggesting that the synthesis of antimicrobial compounds was coupled with both cell growth and cell biomass. In conclusion, the marine lipopeptides-producing B. amyloliquefaciens HY2-1 showed a promising prospect to be explored as a biocontrol agent for plant disease control of crops and postharvest preservation of fruits and vegetables, especially due to its outstanding stress resistance and the broad-spectrum and effective antagonist on various phytopathogenic fungi.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.