Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. PURPOSE: The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. METHODS: In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. RESULTS: The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (ß = 0.07, P = 0.013), penicillin skin test (PST) timing (ß = 0.06, P < 0.001) and medical order timing (ß = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration. CONCLUSIONS: There is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU).

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer.

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.

MLatom 3: A Platform for Machine Learning-Enhanced Computational Chemistry Simulations and Workflows.

Machine learning (ML) is increasingly becoming a common tool in computational chemistry. At the same time, the rapid development of ML methods requires a flexible software framework for designing custom workflows. MLatom 3 is a program package designed to leverage the power of ML to enhance typical computational chemistry simulations and to create complex workflows. This open-source package provides plenty of choice to the users who can run simulations with the command-line options, input files, or with scripts using MLatom as a Python package, both on their computers and on the online XACS cloud computing service at XACScloud.com. Computational chemists can calculate energies and thermochemical properties, optimize geometries, run molecular and quantum dynamics, and simulate (ro)vibrational, one-photon UV/vis absorption, and two-photon absorption spectra with ML, quantum mechanical, and combined models. The users can choose from an extensive library of methods containing pretrained ML models and quantum mechanical approximations such as AIQM1 approaching coupled-cluster accuracy. The developers can build their own models using various ML algorithms. The great flexibility of MLatom is largely due to the extensive use of the interfaces to many state-of-the-art software packages and libraries.

Exploration and Insights on Topology Adjustment of Giant Heterometallic Cages Featuring Inorganic Skeletons Assisted by Machine Learning.

Inorganic molecular cages are emerging multifunctional molecular-based platforms with the unique merits of rigid skeletons and inherited properties from constituent metal ions. However, the sensitive coordination bonds and vast synthetic space have limited their systematic exploration. Herein, two giant cage-like clusters featuring the organic ligand-directed inorganic skeletons of Ni4[La74Ni104(IDA)96(OH)184(C2O4)12(H2O)76]·(NO3)38·(H2O)120 (La74Ni104, 5 × 5 × 3 - C2O4) and [La84Ni132(IDA)108(OH)168(C2O4)24(NO3)12(H2O)116]·(NO3)72·(H2O)296 (La84Ni132, 5 × 5 × 5 - C2O4) were discovered by a high-throughput synthetic search. With the assistance of machine learning analysis of the experimental data, phase diagrams of the two clusters in a four-parameter synthetic space were depicted. The effect of alkali, oxalate, and other parameters on the formation of clusters and the mechanism regulating the size of two n × m × l clusters were elucidated. This work uses high-throughput synthesis and machine learning methods to improve the efficiency of 3d-4f cluster discovery and finds the highest-nuclearity 3d-4f cluster to date by regulating the size of the n × m × l inorganic cages through oxalate ions, which pushes the synthetic methodology study on elusive inorganic giant cages in a significantly systematic way.

A Randomized Clinical Trial to Compare Three Different Methods for Estimating Orogastric Tube Insertion Length in Newborns: A Single-Center Experience in China.

Background: Orogastric (OG) and nasogastric (NG) tubes are frequently used in the NICU. Obtaining a relatively accurate estimated length before insertion could significantly reduce complications. While previous studies have mainly focused on the NG tube, OG tubes are more commonly used in China. Purpose: The objective was to determine whether there were differences in the rate of accurate placement among the adapted nose-ear-xiphoid (NEX) method, nose-ear-midway to the umbilicus (NEMU) method, and weight-based (WB) equation in estimating the OG tube insertion distance. Methods: A randomized, controlled, open-label clinical trial to compare the three methods was conducted in a single center. After enrollment, newborns were randomly assigned into three groups. By radiological assessment, the anatomical region for OG tube placement was analyzed. The primary metric was the tip within the gastric body, and the second metric was strictly accurate placement defined as the tube was not looped back within the stomach and the end was located more than 2 cm but less than 5 cm into the stomach, referred to as T10. Results: This study recruited 156 newborns with the majority being preterm infants (n = 96; 61.5 percent), with an average birth weight of 2,200.8 ± 757.8 g. For the WB equation, 96.2 percent (50 cases) of the OG tubes were placed within the stomach, and the rates were 78.8 percent (41 cases) in the adapted NEX and NEMU methods. The strictly accurate placement rates were highest for the WB equation at 80.8 percent (42/52), followed by the adapted NEX method at 65.4 percent (34/52), and the NEMU method at 57.7 percent (30/52). Conclusion: The WB equation for estimating the insertion depth of the OG tube in newborn infants resulted in more precise placement compared to the adapted NEX and NEMU methods.

Visualizing Chain Growth of Polytelluoxane via Polymerization Induced Emission.

Visualizing polymer chain growth is always a hot topic for tailoring structure-function properties in polymer chemistry. However, current characterization methods are limited in their ability to differentiate the degree of polymerization in real-time without isolating the samples from the reaction vessel, let alone to detect insoluble polymers. Herein, a reliable relationship is established between polymer chain growth and fluorescence properties through polymerization induced emission. (TPE-C2)2 -Te is used to realize in situ oxidative polymerization, leading to the aggregation of fluorophores. The relationship between polymerization degree of growing polytelluoxane (PTeO) and fluorescence intensity is constructed, enabling real-time monitoring of the polymerization reaction. More importantly, this novel method can be further applied to the observation of the polymerization process for growing insoluble polymer via surface polymerization. Therefore, the development of visualization technology will open a new avenue for visualizing polymer chain growth in real-time, regardless of polymer solubility.

A multicentre study on the clinical characteristics of newborns infected with coronavirus disease 2019 during the omicron wave.

Objective: To investigate the clinical characteristics and outcomes of newborns infected with coronavirus disease 2019 (COVID-19) during the Omicron wave. Methods: From December 1, 2022, to January 4, 2023, clinical data were collected from neonates with COVID-19 who were admitted to 10 hospitals in Foshan City, China. Their epidemiological histories, clinical manifestations and outcomes were analysed. The neonates were divided into symptomatic and asymptomatic groups. The t test or χ2 test was used for comparisons between groups. Results: A total of 286 children were diagnosed, including 166 males, 120 females, 273 full-term infants and 13 premature infants. They were 5.5 (0-30) days old on average when they were admitted to the hospital. These children had contact with patients who tested positive for COVID-19 and were infected through horizontal transmission. This study included 33 asymptomatic and 253 symptomatic patients, among whom 143 were diagnosed with upper respiratory tract infections and 110 were diagnosed with pneumonia. There were no severe or critical patients. Fever (220 patients) was the most common clinical manifestation, with a duration of 1.1 (1-6) days. The next most common clinical manifestations were cough with nasal congestion or runny nose (4 patients), cough (34 patients), poor appetite (7 patients), shortness of breath (15 patients), and poor general status (1 patient). There were no significant abnormalities in routine blood tests among the neonates infected with COVID-19 except for mononucleosis. However, compared with the asymptomatic group, in the symptomatic group, the leukocyte and neutrophil granulocyte counts were significantly decreased, and the monocyte count was significantly increased. C-reactive protein (CRP) levels were significantly increased (≥10 mg/L) in 9 patients. Myocardial enzyme, liver function, kidney function and other tests showed no obvious abnormalities. Conclusions: In this study, neonates infected with the Omicron variant were asymptomatic or had mild disease. Symptomatic patients had lower leucocyte and neutrophil levels than asymptomatic patients.

Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial.

BACKGROUND & AIMS: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120). METHODS: This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. RESULTS: A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups. CONCLUSIONS: BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov: NCT03085277.

The Role of Albumin in the Diagnosis of Neonatal Sepsis Over the Last 11 Years: A Retrospective Study.

Background: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together. Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy. Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P<0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB. Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.

Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance.

Polymerization inside living cells provides chemists with a multitude of possibilities to modulate cell activities. Considering the advantages of hyperbranched polymers, such as a large surface area for target sites and multilevel branched structures for resistance to the efflux effect, we reported a hyperbranched polymerization in living cells based on the oxidative polymerization of organotellurides and intracellular redox environment. The intracellular hyperbranched polymerization was triggered by reactive oxygen species (ROS) in the intracellular redox microenvironment, effectively disrupting antioxidant systems in cells by an interaction between Te (+4) and selenoproteins, thus inducing selective apoptosis of cancer cells. Importantly, the obtained hyperbranched polymer aggregated into branched nanostructures in cells, which could effectively evade drug pumps and decrease drug efflux, ensuring the polymerization for persistent treatment. Finally, in vitro and in vivo studies confirmed that our strategy presented selective anticancer efficacy and well biosafety. This approach provides a way for intracellular polymerization with desirable biological applications to regulate cell activities.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Interpretable Machine Learning of Two-Photon Absorption.

Molecules with strong two-photon absorption (TPA) are important in many advanced applications such as upconverted laser and photodynamic therapy, but their design is hampered by the high cost of experimental screening and accurate quantum chemical (QC) calculations. Here a systematic study is performed by collecting an experimental TPA database with ≈900 molecules, analyzing with interpretable machine learning (ML) the key molecular features explaining TPA magnitudes, and building a fast ML model for predictions. The ML model has prediction errors of similar magnitude compared to experimental and affordable QC methods errors and has the potential for high-throughput screening as additionally validated with the new experimental measurements. ML feature analysis is generally consistent with common beliefs which is quantified and rectified. The most important feature is conjugation length followed by features reflecting the effects of donor and acceptor substitution and coplanarity.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Water-Enhanced and Remote Self-Healing Elastomers in Various Harsh Environments.

The development of underwater remote stimulus-responsive self-healing polymer materials for applications in inaccessible and urgent situations is very challenging because water can readily disturb traditional noncovalent bonds and absorb heat, UV light, IR light, and electromagnetic wave energy at the wave band of micrometers and millimeters. Herein, visible-light-responsive diselenide bonds are employed as the healing moieties to produce a water-enhanced and remote self-healing elastomer triggered by a blue laser, which possesses excellent underwater transmission capability. During healing, the strain at break reaches ∼200% in 5 min and its toughness almost fully recovers within 1 h, which is estimated to be the fastest reported to date for healing silicone elastomers with a healing efficiency above 90%. The remote underwater pipeline sealing is instantly accomplished with the diselenide-containing elastomers by a blue laser 3 m away, thereby providing a direction for future emergent healing applications.

Copper-Selenocysteine Quantum Dots for NIR-II Photothermally Enhanced Chemodynamic Therapy.

Chemodynamic therapy has been appealing for effective cancer treatment. Particularly, Fenton-like reactions catalyzed by Cu2+-based nanoparticles showed promising prospects. Herein, we fabricated copper-selenocysteine quantum dots (Cu-Sec QDs) with the majority of Cu+ by a facile and robust thermal titration process. No high temperature or pressure is needed for this synthetic route of QDs. The selenocysteine functioned as the reducing agent as well as the stabilizer, circumventing the poor water solubility and stability, leading to enhanced biocompatibility. The existence of Cu+ endowed the QDs the ability to catalyze the Fenton-like reaction without an extra reduction reaction of Cu2+ to Cu+. Moreover, the strong absorption in the near-infrared-II region (1000-1300 nm) of the final Cu-Sec QDs is in great favor of the chemodynamic therapy via the photothermally enhanced Fenton-like reaction. And the Cu-Sec QDs exhibited obvious cytotoxicity to various cancer cell lines. We believe that this facile and robust synthetic approach could open up another method for the fabrication of quantum dots toward the potential Fenton-like reaction-based applications in biological fields.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

LncRNA CCAT1 promotes prostate cancer cells proliferation, migration, and invasion through regulation of miR-490-3p/FRAT1 axis.

Prostate cancer (PCa) is a prevalent cancer in males, with high incidence and mortality. Recent studies have shown the crucial role of long non-coding RNA (lncRNA) in PCa. Here, we aimed to explore the functional roles and inner mechanisms of lncRNA CCAT1 in PCa cells. qRT-PCR results showed that CCAT1 was upregulated in PCa tissues and cells. Functional assays demonstrated that CCAT1 knockdown suppressed cell proliferation, migration, invasion, yet promoted apoptosis, while CCAT1 promotion showed the opposite results. We also found that CCAT1 negatively regulated miR-490-3p expression and subsequently regulated FRAT1 expression. Inhibition of miR-490-3p or up-regulation of FRAT1 reversed the suppressive effects of CCAT1 knockdown on the PCa cells. In conclusion, CCAT1 regulated FRAT1 expression through miR-490-3p and then promote the PCa cells proliferation, migration, and invasion, which reveals the oncogenic function of CCAT1 in PCa progress.

Neighboring Zn-Zr Sites in a Metal-Organic Framework for CO2 Hydrogenation.

ZrZnOx is active in catalyzing carbon dioxide (CO2) hydrogenation to methanol (MeOH) via a synergy between ZnOx and ZrOx. Here we report the construction of Zn2+-O-Zr4+ sites in a metal-organic framework (MOF) to reveal insights into the structural requirement for MeOH production. The Zn2+-O-Zr4+ sites are obtained by postsynthetic treatment of Zr6(µ3-O)4(µ3-OH)4 nodes of MOF-808 by ZnEt2 and a mild thermal treatment to remove capping ligands and afford exposed metal sites for catalysis. The resultant MOF-808-Zn catalyst exhibits >99% MeOH selectivity in CO2 hydrogenation at 250 °C and a high space-time yield of up to 190.7 mgMeOH gZn-1 h-1. The catalytic activity is stable for at least 100 h. X-ray absorption spectroscopy (XAS) analyses indicate the presence of Zn2+-O-Zr4+ centers instead of ZnmOn clusters. Temperature-programmed desorption (TPD) of hydrogen and H/D exchange tests show the activation of H2 by Zn2+ centers. Open Zr4+ sites are also critical, as Zn2+ centers supported on Zr-based nodes of other MOFs without open Zr4+ sites fail to produce MeOH. TPD of CO2 reveals the importance of bicarbonate decomposition under reaction conditions in generating open Zr4+ sites for CO2 activation. The well-defined local structures of metal-oxo nodes in MOFs provide a unique opportunity to elucidate structural details of bifunctional catalytic centers.

Oxidative Polymerization in Living Cells.

Intracellular polymerization is an emerging technique that can potentially modulate cell behavior, but remains challenging because of the complexity of the cellular environment. Herein, taking advantage of the chemical properties of organotellurides and the intracellular redox environment, we develop a novel oxidative polymerization reaction that can be conducted in cells without external stimuli. We demonstrate that this polymerization reaction is triggered by the intracellular reactive oxygen species (ROS), thus selectively proceeding in cancer cells and inducing apoptosis via a unique self-amplification mechanism. The polymerization products are shown to disrupt intracellular antioxidant systems through interacting with selenoproteins, leading to greater oxidative stress that would further the oxidative polymerization and eventually activate ROS-related apoptosis pathways. The selective anticancer efficacy and biosafety of our strategy are proven both in vitro and in vivo. Ultimately, this study enables a new possibility for chemists to manipulate cellular proliferation and apoptosis through artificial chemical reactions.