Attributable mortality of acute kidney injury among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. METHODS: The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. RESULTS: Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI -5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI -3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p < 0.001), respectively. Particularly noteworthy was that stage 3 AKI emerged as an independent risk factor for 30-day mortality, possessing an adjusted hazard ratio of 1.80 (95% CI 1.31 ∼ 2.47, p < 0.001). CONCLUSIONS: The overall 30-day attributable mortality of AKI among critically ill patients with sepsis was 6.6%. Stage 3 AKI had the most significant contribution to 30-day mortality, while stage 1 and stage 2 AKI did not increase excess mortality.

Transcriptome analysis and functional verification reveal the roles of copper in resistance to potato virus Y infection in tobacco.

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.

Failure of Topological Invariants in Strongly Correlated Matter.

We show exactly that standard "invariants" advocated to define topology for noninteracting systems deviate strongly from the Hall conductance whenever the excitation spectrum contains zeros of the single-particle Green's function, G, as in general strongly correlated systems. Namely, we show that if the chemical potential sits atop the valence band, the "invariant" changes without even accessing the conduction band but by simply traversing the band of zeros that might lie between the two bands. Since such a process does not change the many-body ground state, the Hall conductance remains fixed. This disconnect with the Hall conductance arises from the replacement of the Hamiltonian, h(k), with G^{-1} in the current operator, thereby laying plain why perturbative arguments fail.

Circ_LAS1L regulates cardiac fibroblast activation, growth, and migration through miR-125b/SFRP5 pathway.

Current studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) are closely related in acute myocardial infarction (AMI). Previous studies have shown that miR-125b promotes fibrosis and up-regulates in cardiac fibroblasts (CFs), and further experiments showed that circ_LAS1L had multiple binding sites of miR-125b, and their expression was inversely related in AMI patients and CFs. RNA immunoprecipitation (RIP), pull down, and dual luciferase reporter gene assay all confirmed that miR-125b directly bound to circ_LAS1L. Circ_LAS1L overexpression promoted the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), inhibited the expression of alpha-SMA, collagen I, and collagen III, inhibited CF proliferation and migration, and promoted apoptosis. When cotransfected with circ_LAS1L overexpression vector and miR-125b mimics, the above gene expression and CF biological behaviours did not change significantly. But when cotransfected with circ_LAS1L overexpression vector and SFRP5 siRNA, SFRP5 expression was still down-regulated, the expression of alpha-SMA, collagen I, and collagen III was up-regulated, and the proliferation and migration of CFs were increased. Therefore, circ_LAS1L inhibits the activity of miR-125b by adsorbing it, thus promoting the expression of SFRP5 and then regulating the biological characteristics of CFs. These findings may provide an important experimental basis for the regulation of myocardial fibrosis after myocardial infarction. SIGNIFICANCE OF THE STUDY: Studies have shown that circular RNAs (circRNAs) play important roles in cardiovascular diseases, but there are few studies on their roles in the process of myocardial fibrosis. In this study, we found that circ_LAS1L was down-regulated in acute myocardial infarction (AMI) patients and cardiac fibroblasts (CFs), and could bind directly to miR-125b, thereby promoting the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), ultimately inhibiting the activation, proliferation and migration of CF, and promoting apoptosis. This suggests that circ_LAS1L/miR-125b/SFRP5 pathway can regulate the biological function of CF and may play an important role in the process of myocardial fibrosis, thus providing an important theoretical basis for the regulation of myocardial fibrosis after myocardial infarction.

Additive anticancer effects of chrysin and low dose cisplatin in human malignant glioma cell (U87) proliferation and evaluation of the mechanistic pathway.

PURPOSE: To evaluate the anticancer effect of chrysin and its additive combination with low-dose cisplatin in human glioma (U87) cancer cells and to study its underlying mechanism. METHODS: Inverted phase and fluorescence microscopic studies were done to demonstrate the effect of chrysin and its combination with cisplatin on cellular morphology and apoptosis. Annexin V-FITC assay was used to quantify the extent of apoptosis in chrysin and chrysin+cisplatin treated cells. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of chrysin and its combination with cisplatin on cell cycle phase distribution. RESULTS: The results showed chrysin brought about a potent and dose-dependent antiproliferative effect in human glioma cancer cells. However, the combination of chrysin with low dose cisplatin led to a much higher growth inhibitory effects indicating an additive effect between the two compounds. The combined effect of chrysin and cisplatin also gave rise to a greater apoptosis induction as well as cell cycle arrest in comparison to the treatment by chrysin or cisplatin alone. Fluorescence microscopy as well as inverted phase contrast microscopy also revealed that the combination of chrysin plus cisplatin resulted in greater apoptosis induction as well as cell morphology alterations. Combination treatment of chrysin and cisplatin resulted in greater percentage of cells in early as well as in late apoptotic stages. The combination effect was also seen in mitochondrial membrane potential loss. CONCLUSION: Chrysin additively potentiates the antiproliferative, cell cycle arrest and apoptotic activity of cisplatin in human glioma cancer (U87) cells.

Sorafenib-Encapsulated Liposomes to Activate Hypoxia-Sensitive Tirapazamine for Synergistic Chemotherapy of Hepatocellular Carcinoma.

Combination therapy with the synergistic effect is an effective way in cancer chemotherapy. Herein, an antiangiogenic sorafenib (SOR) and hypoxia-activated prodrug tirapazamine (TPZ)-coencapsulated liposome (LipTPZ/SOR) is prepared for chemotherapy of hepatocellular carcinoma (HCC). SOR is a multi-target tyrosine kinase inhibitor that can inhibit tumor cell proliferation and angiogenesis. The antiangiogenesis effect of SOR can reduce oxygen supply and aggravate tumor hypoxia, which is able to activate hypoxia-sensitive prodrug TPZ, exhibiting the synergistic antitumor effect. LipTPZ/SOR at different molar ratios of TPZ and SOR can significantly inhibit the proliferation of hepatocellular carcinoma cells. The mole ratio of TPZ and SOR was optimized to 2:1, which exhibited the best synergetic antitumor effect. The synergistic antitumor mechanism of SOR and TPZ was also investigated in vivo. After treated with SOR, the number of vessels was decreased, and the degree of hypoxia was aggravated in tumor tissues. What is more, in the presence of SOR, TPZ could be activated to inhibit tumor growth. The combination of TPZ and SOR exhibited an excellent synergistic antitumor effect. This research not only provides an innovative strategy to aggravate tumor hypoxia to promote TPZ activation but also paints a blueprint about a new nanochemotherapy regimen for the synergistic chemotherapy of HCC, which has excellent biosafety and bright clinical application prospects.

Fluorine-Free, Highly Durable Waterproof and Breathable Fibrous Membrane with Self-Clean Performance.

Lightweight, durable waterproof and breathable membranes with multifunctional properties that mimic nature have great potential for application in high-performance textiles, efficient filtering systems and flexible electronic devices. In this work, the fluoride-free triblock copolymer poly(styrene-b-butadiene-b-styrene) (SBS) fibrous membrane with excellent elastic performance was prepared using electrospinning. According to the bionics of lotus leaves, a coarse structure was built onto the surface of the SBS fiber using dip-coating of silicon dioxide nanoparticles (SiO2 NPs). Polydopamine, an efficient interfacial adhesive, was introduced between the SBS fiber and SiO2 NPs. The hydrophobicity of the modified nanofibrous membrane was highly improved, which exhibited a super-hydrophobic surface with a water contact angle large than 160°. The modified membrane retained super-hydrophobic properties after 50 stretching cycles under 100% strains. Compared with the SBS nanofibrous membrane, the hydrostatic pressure and WVT rate of the SBS/PDA/SiO2 nanofibrous membrane improved simultaneously, which were 84.2 kPa and 6.4 kg·m-2·d-1 with increases of 34.7% and 56.1%, respectively. In addition, the SBS/PDA/SiO2 nanofibrous membrane showed outstanding self-cleaning and windproof characteristics. The high-performance fibrous membrane provides a new solution for personal protective equipment.

1/4 is the new 1/2 when topology is intertwined with Mottness.

In non-interacting systems, bands from non-trivial topology emerge strictly at half-filling and exhibit either the quantum anomalous Hall or spin Hall effects. Here we show using determinantal quantum Monte Carlo and an exactly solvable strongly interacting model that these topological states now shift to quarter filling. A topological Mott insulator is the underlying cause. The peak in the spin susceptibility is consistent with a possible ferromagnetic state at T = 0. The onset of such magnetism would convert the quantum spin Hall to a quantum anomalous Hall effect. While such a symmetry-broken phase typically is accompanied by a gap, we find that the interaction strength must exceed a critical value for this to occur. Hence, we predict that topology can obtain in a gapless phase but only in the presence of interactions in dispersive bands. These results explain the recent quarter-filled quantum anomalous Hall effects seen in moiré systems.

Regulating Al2O3/PAN/PEG Nanofiber Membranes with Suitable Phase Change Thermoregulation Features.

To address the thermal comfort needs of the human body, the development of personal thermal management textile is critical. Phase change materials (PCMs) have a wide range of applications in thermal management due to their large thermal storage capacity and their isothermal properties during phase change. However, their inherent low thermal conductivity and susceptibility to leakage severely limit their application range. In this study, polyethylene glycol (PEG) was used as the PCM and polyacrylonitrile (PAN) as the polymer backbone, and the thermal conductivity was increased by adding spherical nano-alumina (Al2O3). Utilizing coaxial electrospinning technology, phase-change thermoregulated nanofiber membranes with a core-shell structure were created. The study demonstrates that the membranes perform best in terms of thermal responsiveness and thermoregulation when 5% Al2O3 is added. The prepared nanofiber membranes have a melting enthalpy of 60.05 J·g-1 and retain a high enthalpy after 50 cycles of cold and heat, thus withstanding sudden changes in ambient temperature well. Additionally, the nanofiber membranes have excellent air permeability and high moisture permeability, which can increase wearer comfort. As a result, the constructed coaxial phase change thermoregulated nanofiber membranes can be used as a promising textile for personal thermal management.

A Fast Decision Algorithm for VVC Intra-Coding Based on Texture Feature and Machine Learning.

Due to the development and application of information technology, a series of modern information technologies represented by 5G, big data, and artificial intelligence are changing rapidly, and people's requirements for video coding standards have become higher. In the High-Efficiency Video Coding (HEVC) standard, the coding block division is not flexible enough, and the prediction mode is not detailed enough. A new generation of Versatile Video Coding (VVC) standards was born. VVC inherits the hybrid coding framework adopted by HEVC, improves the original technology of each module, introduces a series of new coding technologies, and builds on this greatly improving the coding efficiency. Compared with HEVC, the block division structure of VVC has undergone great changes, retaining the quad-tree (QT) division method and increasing the multi-type tree (MTT) division method, which brings high coding complexity. To reduce the computational complexity of VVC coding block division, a fast decision algorithm for VVC intra-frame coding based on texture characteristics and machine learning is proposed. First, we analyze the characteristics of the CU partition structure decision and then use the texture complexity of the CU partition structure decision to terminate the CU partition process early; for CUs that do not meet the early termination of the partition, use the global sample information, local sample information, and context information. The three-category feature-trained tandem classifier framework predicts the division type of CU. The experimental results show that in the full intra mode, compared with the existing VTM10.0, the encoding output bit rate is increased by 1.36%, and the encoding time is saved by 52.63%.

Recombinant HNP-1 Produced by Escherichia coli Triggers Bacterial Apoptosis and Exhibits Antibacterial Activity against Drug-Resistant Bacteria.

Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical applications have been hampered by challenges during mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that Escherichia coli expressing full-length preproHNP-1 secretes a soluble form of HNP-1, which can be recovered from the total cell lysate after isopropyl thio-ß-d-galactoside (IPTG) induction and ultrafiltration. Label-free quantitative proteomics and co-immunoprecipitation experiments revealed that HNP-1 induces cell apoptosis in bacteria by causing DNA and membrane damage. Notably, we found that HNP-1 disrupts the DNA damage response pathway by interfering with the binding of RecA to single-stranded DNA (ssDNA). Further experiments demonstrated that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results indicated that recombinant protein expression may be a simple and cost-effective solution to produce HNP-1 and that RecA inhibition via HNP-1 may serve as an alternative strategy to counteract antibiotic resistance. IMPORTANCE Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical application has been hampered by the difficulty of mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that recombinant protein expression combined with ultrafiltration may be a simple and cost-effective solution to HNP-1 production. We further found that HNP-1 induces bacterial apoptosis and prevents its SOS repair pathway from binding to the RecA protein, which may be a new antibacterial mechanism. In addition, we showed that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results provide new insights into the production and antibacterial mechanism of HNP-1, both of which may promote its clinical application.

E/D-Mode GaN Inverter on a 150-mm Si Wafer Based on p-GaN Gate E-Mode HEMT Technology.

AlGaN/GaN E/D-mode GaN inverters are successfully fabricated on a 150-mm Si wafer. P-GaN gate technology is applied to be compatible with the commercial E-mode GaN power device technology platform and a systematic study of E/D-mode GaN inverters has been conducted with detail. The key electrical characters have been analyzed from room temperature (RT) to 200 °C. Small variations of the inverters are observed at different temperatures. The logic swing voltage of 2.91 V and 2.89 V are observed at RT and 200 °C at a supply voltage of 3 V. Correspondingly, low/high input noise margins of 0.78 V/1.67 V and 0.68 V/1.72 V are observed at RT and 200 °C. The inverters also demonstrate small rising edge time of the output signal. The results show great potential for GaN smart power integrated circuit (IC) application.

Shape Tuning and Size Prediction of Millimeter-Scale Calcium-Alginate Capsules with Aqueous Core.

: Controllable feature and size, good mechanical stability and intelligent release behavior is the capsule products relentless pursuit of the goal. In addition, to illustrate the quantitative relationship of structure and performance is also important for encapsulation technology development. In this study, the sphericity and size of millimeter-scale calcium sodium alginate capsules (mm-CaSA-Caps) with aqueous core were well tuned by manipulating the viscosity, surface tension, and density of CaCl2/carboxyl methyl cellulose (CMC) drops and sodium alginate (SA) solution. The well-tuned mm-CaSA-Caps showed significant mechanical and control-releasing property effects. The results showed that the prepared mm-CaSA-Caps were highly monodispersed with average diameter from 3.8 to 4.8 mm. The viscosity of the SA solution and the viscosity and surface tension of the CaCl2/CMC solution had significant effects on the mm-CaSA-Caps sphericity. Uniform and spherical mm-CaSA-Caps could be formed with high viscosity CaCl2/CMC solution (between 168.5 and 917.5 mPa·s), low viscosity SA solution (between 16.2 and 72.0 mPa·s) and decreased surface tension SA solution (by adding 0.01 wt.% poloxamer 407). The diameter of the mm-CaSA-Caps could be predicted by a modified Tate's law, which correlated well with the experimental data. The Caps with sphericity factor (SF) < 0.07 had better mechanical stability, with the crushing force 2.91-15.5 times and the surface Young's modulus 2.1-3.99 times higher than those of the non-spherical Caps (SF > 0.07). Meanwhile, the spherical Caps had a more even permeation rate, which was helpful in producing uniform and sustained releasing applications in foodstuff, medicine, agriculture and chemical industry.

The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis.

It has been suggested that Staufen (Stau) is key in controlling the variability of the posterior boundary of the Hb anterior domain (xHb). However, the mechanism that underlies this control is elusive. Here, we quantified the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, we show that the xHb of stau- mutants reproducibly moves posteriorly by 10% of the embryo length (EL) to the wild type (WT) position in the nuclear cycle (nc) 14, and that its variability over short time windows is comparable to that of the WT. Moreover, for stau- mutants, the upstream Bicoid (Bcd) gradients show equivalent relative intensity noise to that of the WT in nc12-nc14, and the downstream Even-skipped (Eve) and cephalic furrow (CF) show the same positional errors as these factors in WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive and could both be implemented in early Drosophila embryogenesis.

Broadly speaking, all individuals of any animal species share a highly consistent shape and structure. Despite this, the activity of the genes that control these body patterns can vary significantly. There are currently two models that have been proposed for how noisy systems of genes, and the proteins they code, can produce consistent body patterns. The first, suggests the noise is essentially self-compensating so stably produces the same result, while the second invokes localized self-organizing systems that help to refine the structural details. In the early stages of development for the fruit fly, Drosophila melanogaster, one of the proteins that controls body patterns is called Hunchback (often just Hb for short). The Hb proteins are largely found at the front-end of the fly embryo, with a sharp drop near the middle. Normally the position of the drop in Hb varies between flies by around 1% of the total length of the fly embryo. Previous work has linked a gene called staufan (or stau for short) to the distribution of Hb in flies but the mechanism involved is unknown. Yang, Zhu, Kong et al. have now used a technique called light sheet microscopy to accurately measure the location of Hb proteins in fruit fly embryos. Without the stau gene, the average position of the drop in Hb proteins underwent a larger shift towards the rear at a key stage in development. Despite this altered behavior, the extent of variation between flies did not change. Similarly, the variation of other genes that control Hb location and that are controlled by Hb remained unchanged. As such, it seems stau affects Hb positioning but has no impact on variation between individuals. These findings suggest that both models for controlling variation in fly development could still be relevant and may operate together. This study also provides a new method for the more precise measurement of systems like these that may offer insights into the mechanisms involved in early embryonic development.

Bio-based barium alginate film: Preparation, flame retardancy and thermal degradation behavior.

A bio-based barium alginate film was prepared via a facile ionic exchange and casting approach. Its flammability, thermal degradation and pyrolysis behaviors, thermal degradation mechanism were studied systemically by limiting oxygen index (LOI), vertical burning (UL-94), microscale combustion calorimetry (MCC), thermogravimetric analysis (TGA) coupled with Fourier transform infrared analysis (FTIR) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). It showed that barium alginate film had much higher LOI value (52.0%) than that of sodium alginate film (24.5%). Moreover, barium alginate film passed the UL-94 V-0 rating, while the sodium alginate film showed no classification. Importantly, peak of heat release rate (PHRR) of barium alginate film in MCC test was much lower than that of sodium alginate film, suggested that introduction of barium ion into alginate film significantly decreased release of combustible gases. TG-FTIR and Py-GC-MS results indicated that barium alginate produced much less flammable products than that of sodium alginate in whole thermal degradation procedure. Finally, a possible degradation mechanism of barium alginate had been proposed.

Fabrication of interpenetrating polymer network chitosan/gelatin porous materials and study on dye adsorption properties.

One kind of adsorbent based on chitosan and gelatin with interpenetrating polymer networks (IPN) and porous dual structures was prepared using genipin as the cross-linker. These dual structures were demonstrated by means of Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). Adsorptions of acid orange II dye from aqueous solution were carried out at different genipin contents, adsorption times and pH values. The results showed that this material was put up the largest adsorption capacity when the genipin content is 0.25 mmol/L, meanwhile, the lower the solution pH value the greater the adsorption capacity. The chitosan/gelatin interpenetrating polymer networks porous material displayed pH-sensitive and rapidly response in adsorption and desorption to pH altered. It is indicated that the cross-linked chitosan/gelatin interpenetrating polymer networks porous material could be used as a recyclable adsorbent in removal or separation of anionic dyes as environmental pH condition changed.

[Construction of an acellular porcine aortic valve].

OBJECTIVE: To prepare a porcine aortic valve (PAV) free of the cellular components. METHODS: The cellular components of porcine PAV were completely removed using trypsin and Triton X-100, and the acellular PAV was examined microscopically with HE staining with its physical and chemical properties assessed. Transmission electron microscopy was used to observe the integrity of the collagen and elastin and the DNA contents in the PAV was detected to confirm the total removal of the cellular components. With the fresh PAV as the control, small pieces of the acellular PAV were implanted into the subcutaneous tissues of 4 rabbits, and 4 weeks after the implantation, the implants were harvested for microscopic observation. RESULTS: The cellular components were effectively removed from the cusps and roots of the PAV by trypsin and TritonX-100, with marked soluble protein loss [(0.24-/+0.04)% vs (0.48-/+0.12)%] and significantly increased water content [(92.2-/+1.5)% vs (89.2-/+1.6)%]. The acellular PAV still maintained good fibrous scaffold structure and the shrinkage temperature and tension at fracture underwent no significantly changes [(67.9-/+1.0) degrees celsius; vs (68.8-/+0.8) degrees celsius; and (489.3-/+19.0) g/mm2 vs (540.7-/+19.5) g/mm2, respectively]. The PAVs implanted in rabbits showed only mild tissue reaction with a few infiltrating neutrophils, lymphocytes and plasmocytes observed 4 weeks later. The accelular PAV caused obviously milder inflammatory reactions than fresh PAV. CONCLUSIONS: The acellular PAV prepared by treatment with trypsin and Triton X-100 retains good fibrous scaffold structure and mechanical strength with low antigenicity.