Mortality and other clinical outcomes between culture-negative and culture-positive septic patients have been documented inconsistently and are very controversial. A systematic review and ...meta-analysis was performed to compare the clinical outcomes of culture-negative and culture-positive sepsis or septic shock.
We searched the PubMed, Cochrane and Embase databases for studies from inception to the 1st of January 2021. We included studies involving patients with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality and clearly compared culture-negative versus culture-positive patients with clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, mechanical ventilation requirements, mechanical ventilation duration and renal replacement requirements). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).
Seven studies including 22,655 patients were included. The primary outcome of this meta-analysis showed that there was no statistically significant difference in the all-cause mortality between two groups (OR = 0.95; 95% CI, 0.88 to 1.01; P = 0.12; Chi-
= 30.71; I
= 80%). Secondary outcomes demonstrated that there was no statistically significant difference in the ICU length of stay (MD = - 0.19;95% CI, - 0.42 to 0.04; P = 0.10;Chi-
= 5.73; I
= 48%), mechanical ventilation requirements (OR = 1.02; 95% CI, 0.94 to 1.11; P = 0.61; Chi
= 6.32; I
= 53%) and renal replacement requirements (OR = 0.82; 95% CI, 0.67 to 1.01; P = 0.06; Chi-
= 1.21; I
= 0%) between two groups. The hospital length of stay of culture-positive group was longer than that of the culture-negative group (MD = - 3.48;95% CI, - 4.34 to - 2.63; P < 0.00001;Chi-
= 1.03; I
= 0%). The mechanical ventilation duration of culture-positive group was longer than that of the culture-negative group (MD = - 0.64;95% CI, - 0.88 to - 0.4; P < 0.00001;Chi-
= 4.86; I
= 38%).
Culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. Furthermore, culture-positive septic patients had similar ICU length of stay, mechanical ventilation requirements and renal replacement requirements as those culture-negative patients. The hospital length of stay and mechanical ventilation duration of culture-positive septic patients were both longer than that of the culture-negative patients. Further large-scale studies are still required to confirm these results.
Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have ...been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown.
Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p.
In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC.
Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC.
Catalytic transformation of CH
under a mild condition is significant for efficient utilization of shale gas under the circumstance of switching raw materials of chemical industries to shale gas. ...Here, we report the transformation of CH
to acetic acid and methanol through coupling of CH
, CO and O
on single-site Rh
O
anchored in microporous aluminosilicates in solution at ≤150 °C. The activity of these singly dispersed precious metal sites for production of organic oxygenates can reach about 0.10 acetic acid molecules on a Rh
O
site per second at 150 °C with a selectivity of ~70% for production of acetic acid. It is higher than the activity of free Rh cations by >1000 times. Computational studies suggest that the first C-H bond of CH
is activated by Rh
O
anchored on the wall of micropores of ZSM-5; the formed CH
then couples with CO and OH, to produce acetic acid over a low activation barrier.
Direct conversion of methane to chemical feedstocks such as methanol under mild conditions is a challenging but ideal solution for utilization of methane. Pd1O4 single‐sites anchored on the internal ...surface of micropores of a microporous silicate exhibit high selectivity and activity in transforming CH4 to CH3OH at 50–95 °C in aqueous phase through partial oxidation of CH4 with H2O2. The selectivity for methanol production remains at 86.4 %, while the activity for methanol production at 95 °C is about 2.78 molecules per Pd1O4 site per second when 2.0 wt % CuO is used as a co‐catalyst with the Pd1O4@ZSM‐5. Thermodynamic calculations suggest that the reaction toward methanol production is highly favorable compared to formation of a byproduct, methyl peroxide.
Single site Pd1O4 anchored in microspores of zeolite with 2.0 w % CuO is active for transforming of CH4 to CH3OH in aqueous solution in the temperature range of 50–95 °C. Selectivity for production of CH3OH in this temperature range was found to be 78 %‐86 % at 50–95 °C, offering a clear improvement over harsh alternative conditions.
Structural complexity of glycans derived from the diversities in composition, linage, configuration, and branching considerably complicates structural analysis. Nanopore-based single-molecule sensing ...offers the potential to elucidate glycan structure and even sequence glycan. However, the small molecular size and low charge density of glycans have restricted direct nanopore detection of glycan. Here we show that glycan sensing can be achieved using a wild-type aerolysin nanopore by introducing a facile glycan derivatization strategy. The glycan molecule can induce impressive current blockages when moving through the nanopore after being connected with an aromatic group-containing tag (plus a carrier group for the neutral glycan). The obtained nanopore data permit the identification of glycan regio- and stereoisomers, glycans with variable monosaccharide numbers, and distinct branched glycans, either independently or with the use of machine learning methods. The presented nanopore sensing strategy for glycans paves the way towards nanopore glycan profiling and potentially sequencing.
Zwitterionic materials have shown their excellent performance in many biological and chemical applications. Zwitterionic materials possess moieties that own both cationic and anionic groups. The ...associations among zwitterionic moieties through electrostatic interactions play an important role in properties of zwitterionic materials. However, the relationship between the molecular structures and associations of zwitterionic moieties are still not well understood. This work compared thermal- and salt-responsive behaviors of sulfobetaine and carboxybetaine polymers by examining their rheological properties as a function of temperature and their hydrodynamic sizes as a function of salt concentration. Results showed that carboxybetaine polymers do not exhibit stimuli responses as expected from the antipolyelectrolyte behavior of zwitterionic polymers as observed in sulfobetaine polymers. We studied and compared the associations among zwitterionic moieties in these two zwitterionic polymers using molecular dynamic simulations. Simulation results show that the charge-density difference between cationic and anionic groups determines the associations among zwitterionic moieties, which are responsible for different stimuli responses of carboxybetaine and sulfobetaine polymers.
Direct upgrading of methane into value-added products is one of the most significant technologies for the effective transformation of hydrocarbon feedstocks in the chemical industry. Both oxidative ...and non-oxidative methane conversion are broadly useful approaches, though the two reaction pathways are quite distinguished. Oxidative coupling of methane (OCM) has been widely studied, but suffers from the low selectivity to C2 hydrocarbons because of the overoxidation leading to undesired byproducts. Therefore, non-oxidative coupling of methane is a worthy alternative approach to be developed for the efficient, direct utilization of methane. Recently, heterogeneous catalysts comprising singly dispersed metal sites, such as single-atom catalysts (SAC) and surface organometallic catalysts (SOMCat), have been proven to be effectively active for direct coupling of methane to product hydrogen and C2 products. In this context, this review summarizes recent discoveries of these novel catalysts and provides a perspective on promising catalytic processes for methane transformation via non-oxidative coupling.
Photodynamic therapy (PDT), as a novel technique, has been extensively employed in cancer treatment by utilizing reactive oxygen species (ROS) to kill malignant cells. However, most photosensitizers ...(PSs) are short of ROS yield and affect the therapeutic effect of PDT. Thus, there is a substantial demand for the development of novel PSs for PDT to advance its clinical translation. In this study, we put forward a new strategy for PS synthesis via modifying graphene quantum dots (GQDs) on the surface of rare-earth elements doped upconversion nanoparticles (UCNPs) to produce UCNPs@GQDs with core-shell structure. This new type of PSs combined the merits of UCNPs and GQDs and produced ROS efficiently under near-infrared light excitation to trigger the PDT process. UCNPs@GQDs exhibited high biocompatibility and obvious concentration-dependent PDT efficiency, shedding light on nanomaterials-based PDT development.
Small ubiquitin-like modifier (SUMO) binding (termed SUMOylation) emerged as the inducer for the sorting of bioactive molecules into extracellular vesicles (EVs), triggering lymphangiogenesis and ...further driving tumor lymph node (LN) metastasis, but the precise mechanisms remain largely unclear. Here, we show that bladder cancer (BCa) cell-secreted EVs mediated intercellular communication with human lymphatic endothelial cells (HLECs) through transmission of the long noncoding RNA ELNAT1 and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models. Mechanistically, ELNAT1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1 at the lysine 113 residue, which mediated recognition of ELNAT1 by the endosomal sorting complex required for transport (ESCRT) and facilitated its packaging into EVs. EV-mediated ELNAT1 was specifically transmitted into HLECs and epigenetically activated SOX18 transcription to induce lymphangiogenesis. Importantly, blocking the SUMOylation of tumor cells by downregulating UBC9 expression markedly reduced lymphatic metastasis in EV-mediated, ELNAT1-treated BCa in vivo. Clinically, EV-mediated ELNAT1 was correlated with LN metastasis and a poor prognosis for patients with BCa. These findings highlight a molecular mechanism whereby the EV-mediated ELNAT1/UBC9/SOX18 regulatory axis promotes lymphangiogenesis and LN metastasis in BCa in a SUMOylation-dependent manner and implicate ELNAT1 as an attractive therapeutic target for LN metastatic BCa.
Osmoregulation is essential for organisms to adapt to the exterior environment and plays an important role in embryonic organogenesis. Tubular organ formation usually involves a hyperosmotic lumen ...environment. The mechanisms of how the cells respond and regulate lumen formation remain largely unknown. Here, we reported that the nuclear factor of activated T cells-5 (
), the only transcription factor in the
family involved in the cellular responses to hypertonic stress, regulated notochord lumen formation in chordate
.
(
-
) was expressed in notochord, and its expression level increased during notochord lumen formation and expansion. Knockout and expression of the dominant negative of
in
embryos resulted in the failure of notochord lumen expansion. We further demonstrated that the
-NFAT5 transferred from the cytoplasm into nuclei in HeLa cells under the hyperosmotic medium, indicating
can respond the hypertonicity. To reveal the underly mechanisms, we predicted potential downstream genes of
and further validated
interacted genes by the luciferase assay. The results showed that
NFAT5 promoted
expression. Furthermore, expression of a transport inactivity mutant of
(L421P) in notochord led to the failure of lumen expansion, phenocopying that of
knockout. These results suggest that
-
regulates notochord lumen expansion via the SLC26A6 axis. Taken together, our results reveal that the chordate
responds to hypertonic stress and regulates lumen osmotic pressure via an ion channel pathway on luminal organ formation.
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