Enhanced Catalytic Activity of Crystalline Phosphorus Nanosheets Fabricated via Solvothermal Phase Transformation.

The newly reported crystalline phosphorus nanosheets (cryst-P NSs) exhibit promising features for industrial applications, including outstanding air-water stability and facile large-scale production. However, their complex crystallization impedes a priori tailoring. Herein, the temporal evolution of cryst-P NSs was investigated with the optimized synthesis parameters. The occurrence of self-assembly and solid-state rearrangement unveiled the existence of an intermediate phase as the bulk crystalline precursor and the predominance of nonclassical crystallization pathway(s). With the upgraded synthesis protocol simultaneously strengthening the merits of cryst-P NSs, their catalytic performances were evaluated in various electro- and/or photocatalytic reactions spanning hydrogen and oxygen evolution, full water splitting, CO2 reduction, and organic pollutant decomposition. Superior catalytic activities and orders of magnitude longer lifetimes were consistently discerned compared with the widely employed black phosphorus nanosheets with similar size and thickness. The exciting discoveries in both fundamental crystallization and catalytic applications drastically thrust the comprehension of elemental phosphorus, shedding light on the encouraging capabilities of solvothermal synthesis strategies in the design and systematic tailoring of phosphorus materials.

Identifying high-risk multiple myeloma patients: A novel approach using a clonal gene signature.

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS demonstrated higher performance in identifying high-risk patients compared to the GEP70 and SKY92 signatures recommended for prognostic stratification of MM. CGS can further stratify patients into subgroups with significantly differential prognoses when applied to the high- and low-risk groups identified by GEP70 and SKY92. Additionally, CGS scores are significantly associated with patient response to dexamethasone, a commonly used treatment for MM. In summary, we proposed a computational framework that requires only gene expression data to identify CGSs for prognosis prediction. CGS provides a useful biomarker for improving prognostic stratification in MM, especially for identifying the highest-risk patients.

Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1.

BACKGROUND: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants. METHODS: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 µg/mL and 4 µg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives. FINDINGS: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 µg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 µg/mL and 4 µg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data. INTERPRETATION: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.

Operando Spectroscopic Elucidation of the Bubble Sunshade Effect in Inorganic-Biological Hybrids for Photosynthetic Hydrogen Production.

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

Pt-O-Ce interaction enhanced by Al substitution to promote the acetone degradation through accelerating the breaking of CC bond in acetic acid intermediate.

The reaction rate of volatile organic compounds (VOCs) oxidation is controlled by the rate-limiting step in the total reaction process. This study proposes a novel strategy, by which the rate-limiting step of acetone oxidation is accelerated by enhanced chemical bond interaction with more electrons transfer through Al-substituted CeO2 loaded Pt (Pt/Al-CeO2). Results indicate that the rate-limiting step in the process of acetone oxidation is the decomposition of acetic acid. Al substitution enhances the Pt-O-Ce interaction that transfers more electrons from Pt/Al-CeO2 to acetic acid, promoting the breaking of its CC bond with a lower free energy barrier. Attributing to these, the reaction rate of Pt/Al-CeO2 is 13 times as high as that of Pt/CeO2 and its TOFPt value is 11 times as high as that of Pt/CeO2 at 150 °C. Moreover, the CO2 selectivity of Pt/Al-CeO2 also increases by 22 %. This work establishes the relationship between Pt-O-Ce interaction and acetone oxidation that provides novel perspectives on the development of efficient materials for VOCs oxidation.

Three-Dimensional Bimetallic Ammonium K-Eu Nitrate with a Rare (6,6)-Connected Ion Topology Exhibiting Structural Phase Transition and Photoluminescence Properties.

A K-Eu bimetallic ammonium metal-nitrate three-dimensional (3D) framework incorporating R-N-methyl-3-hydroxyquinuclidine, (RM3HQ)2KEu(NO3)6 (RM3HQ = R-N-methyl-3-hydroxyquinuclidine, 1), was characterized and reported. Distinguishing from the former hybrid rare-earth double perovskites, 1 adopts a mixed corner- and face-sharing K+/Eu3+-centered polyhedral connectivity to form a 3D inorganic framework, showing a rare (6, 6)-connected ion topology with a 66 framework. Notably, 1 exhibits clear phase transition, and the switchable thermodynamic behavior is confirmed by variable-temperature dielectric measurements and second-harmonic generation response. Moreover, 1 also shows photoluminescence properties. The activator Eu3+ plays a crucial role in this process, leading to a significant narrow emission at 592 nm with a photoluminescence quantum yield (PLQY) of 20.76%. The fluorescence lifetime (FLT) of 1 is 4.32 ms. This finding enriches the bimetallic hybrid system for potential electronic and/or luminescence applications.

Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Weight status changes from childhood to adulthood were associated with cardiometabolic outcomes in adulthood.

AIM: Few studies have assessed the association between weight changes from childhood to adulthood and cardiometabolic factors in adulthood. The aim of this study was to explore the relationships between weight changes from childhood to adulthood and cardiometabolic factors in adulthood using national Chinese data. METHODS: We included 649 participants from the China Health and Nutrition Survey from 1989 to 2009 and divided them into four groups by their body mass index from 6 to 37 years of age. They were selected using multistage random cluster sampling from 15 areas with large variations in economic and social development. Poisson regression models assessed associations between weight status changes and cardiometabolic outcomes in adulthood. RESULTS: The risk of multiple abnormal cardiometabolic outcomes in adulthood was increased in the 126 subjects with normal weight in childhood but overweight or obesity in adulthood and the 28 with obesity at both ages, compared to the 462 with normal weight at both ages. There was insufficient evidence to demonstrate that the 33 who had weight issues as children, but not as adults, had an increased risk. CONCLUSION: Being overweight or obese in both childhood and adulthood or during adulthood only increased the risk of abnormal cardiometabolic outcomes in adulthood. Larger studies need to investigate whether weight problems in childhood, but not adulthood, increase the risk.

Association of common maternal infections with birth outcomes: a multinational cohort study.

PURPOSE: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. METHODS: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. RESULTS: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. CONCLUSION: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.

Artificial intelligence powered advancements in upper extremity joint MRI: A review.

Magnetic resonance imaging (MRI) is an indispensable medical imaging examination technique in musculoskeletal medicine. Modern MRI techniques achieve superior high-quality multiplanar imaging of soft tissue and skeletal pathologies without the harmful effects of ionizing radiation. Some current limitations of MRI include long acquisition times, artifacts, and noise. In addition, it is often challenging to distinguish abutting or closely applied soft tissue structures with similar signal characteristics. In the past decade, Artificial Intelligence (AI) has been widely employed in musculoskeletal MRI to help reduce the image acquisition time and improve image quality. Apart from being able to reduce medical costs, AI can assist clinicians in diagnosing diseases more accurately. This will effectively help formulate appropriate treatment plans and ultimately improve patient care. This review article intends to summarize AI's current research and application in musculoskeletal MRI, particularly the advancement of DL in identifying the structure and lesions of upper extremity joints in MRI images.

Gas-Liquid Interface Route to Hybrid Copper Bromine Perovskite Single-Crystal Membrane with Dielectric Transitions and Ferromagnetic Exchanges.

Single-crystal membranes (SCMs) show great promise in the fields of sensors, light-emitting diodes, and photodetection. However, the growth of a large-area single-crystal membranes is challenging. We report a new organic-inorganic SCMs [HCMA]2CuBr4 (HCMA = cyclohexanemethylamine) crystallized at the gas-liquid interface. It also has low-temperature ferromagnetic order, high-temperature dielectric anomalies, and narrow band gap indirect semiconductor properties. Specifically, the reversible phase transition of the compound occurs at 350/341 K on cooling/heating and exhibits dielectric anomalies and stable switching performance near the phase transition temperature. The ferromagnetic exchange interaction in the inorganic octahedra and the organic layer enables ferromagnetic ordering at low-temperature 10 K. Finally, the single crystal exhibits an indirect semiconducting property with a narrow band gap of 0.99 eV. Such rich multichannel physical properties make it a potential application in photodetection, information storage and sensors.

Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway.

BACKGROUND: Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD. The present research aims to explore the potential neuroprotective properties of APHD and its underlying mechanisms. METHODS: The possible mechanism of APHD was predicted using a combination of molecular docking and network pharmacological analysis. PC12 cells were induced by H2O2 and oxygen-glucose deprivation/reoxygenation (OGD/R), respectively. Western blot, flow cytometry, immunofluorescence staining, and qRT-PCR were used to investigate the antioxidant activity of APHD. The HO-1 inhibitor ZnPP and Nrf2 gene silencing were employed to confirm the influence of APHD on the signaling cascade involving HO-1, Nrf2, and Keap1 in vitro. RESULTS: APHD exhibited antioxidant activity in both PC12 cells subjected to H2O2 and OGD/R conditions by downregulating the release of LDH, the concentrations of MDA, and ROS, and upregulating SOD, GSH-Px, and GSH concentrations. APHD could potentially initiate the Keap1-Nrf2/HO-1 signaling cascade, according to the findings from network pharmacology evaluation and molecular docking. Furthermore, APHD was observed to increase Nrf2 and HO-1 expression at both mRNA and protein levels, while downregulating the protein concentrations of Keap1. Both Nrf2 silencing and treatment with ZnPP reversed the neuroprotective effects of APHD. CONCLUSIONS: APHD activated antioxidant enzymes and downregulated the levels of LDH, MDA, and ROS in two cell models. The neuroprotective effect is presumably reliant on upregulation of the Keap1-Nrf2/HO-1 pathway. Taken together, APHD from brown algae of the genus Dictyota shows potential as a candidate for novel neuroprotective agents.

Rare-Earth Metal-Organic Framework with Nonplanar Porphyrin Groups for High-Efficiency Photocatalysis.

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer.

Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Evaluation of Open-Source Large Language Models for Metal-Organic Frameworks Research.

Along with the development of machine learning, deep learning, and large language models (LLMs) such as GPT-4 (GPT: Generative Pre-Trained Transformer), artificial intelligence (AI) tools have been playing an increasingly important role in chemical and material research to facilitate the material screening and design. Despite the exciting progress of GPT-4 based AI research assistance, open-source LLMs have not gained much attention from the scientific community. This work primarily focused on metal-organic frameworks (MOFs) as a subdomain of chemistry and evaluated six top-rated open-source LLMs with a comprehensive set of tasks including MOFs knowledge, basic chemistry knowledge, in-depth chemistry knowledge, knowledge extraction, database reading, predicting material property, experiment design, computational scripts generation, guiding experiment, data analysis, and paper polishing, which covers the basic units of MOFs research. In general, these LLMs were capable of most of the tasks. Especially, Llama2-7B and ChatGLM2-6B were found to perform particularly well with moderate computational resources. Additionally, the performance of different parameter versions of the same model was compared, which revealed the superior performance of higher parameter versions.

Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing.

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.