Single cobalt atoms anchored on Ti3C2Tx with dual reaction sites for efficient adsorption-degradation of antibiotic resistance genes.

The assimilation of antibiotic resistance genes (ARGs) by pathogenic bacteria poses a severe threat to public health. Here, we reported a dual-reaction-site-modified CoSA/Ti3C2Tx (single cobalt atoms immobilized on Ti3C2Tx MXene) for effectively deactivating extracellular ARGs via peroxymonosulfate (PMS) activation. The enhanced removal of ARGs was attributed to the synergistic effect of adsorption (Ti sites) and degradation (Co-O3 sites). The Ti sites on CoSA/Ti3C2Tx nanosheets bound with PO43- on the phosphate skeletons of ARGs via Ti-O-P coordination interactions, achieving excellent adsorption capacity (10.21 × 1010 copies mg-1) for tetA, and the Co-O3 sites activated PMS into surface-bond hydroxyl radicals (•OHsurface), which can quickly attack the backbones and bases of the adsorbed ARGs, resulting in the efficient in situ degradation of ARGs into inactive small molecular organics and NO3. This dual-reaction-site Fenton-like system exhibited ultrahigh extracellular ARG degradation rate (k > 0.9 min-1) and showed the potential for practical wastewater treatment in a membrane filtration process, which provided insights for extracellular ARG removal via catalysts design.

Decoupled responses of above- and below-ground beta-diversity to nitrogen enrichment in a typical steppe.

Increased atmospheric nitrogen (N) deposition affects biodiversity in terrestrial ecosystems. However, we do not know whether the effects of N on above-ground plant ß-diversity are coupled with changes occurring in the soil seed bank. We conducted a long-term N-addition experiment in a typical steppe and found that above-ground ß-diversity increased and then decreased with increasing N addition, whereas below-ground ß-diversity decreased linearly. This suggests decoupled dynamics of plant communities and their soil seed bank under N enrichment. Species substitution determined above- and below-ground ß-diversity change via an increasing role of deterministic processes with N addition. These effects were mostly driven by differential responses of the above-ground vegetation and the soil seed bank ß-diversities to N-induced changes in environmental heterogeneity, increased soil inorganic N concentrations and soil acidification. Our findings highlight the importance of considering above- and below-ground processes simultaneously for effectively conserving grassland ecosystems under N enrichment.

Unlocking Mixed-Metal Oxides Active Centers via Acidity Regulation for K&SO2 Poisoning Resistance: Self-Detoxification Mechanism of Zeolite-Confined deNOx Catalysts.

Selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3-SCR) is an efficient NOx reduction strategy, while the denitrification (deNOx) catalysts suffer from serious deactivation due to the coexistence of multiple poisoning substances, such as alkali metal (e.g., K), SO2, etc., in industrial flue gases. It is essential to understand the interaction among various poisons and their effects on the deNOx process. Herein, the ZSM-5 zeolite-confined MnSmOx mixed (MnSmOx@ZSM-5) catalyst exhibited better deNOx performance after the poisoning of K, SO2, and/or K&SO2 than the MnSmOx and MnSmOx/ZSM-5 catalysts, the deNOx activity of which at high temperature (H-T) increased significantly (>90% NOx conversion in the range of 220-480 °C). It has been demonstrated that K would occupy both redox and acidic sites, which severely reduced the reactivity of MnSmOx/ZSM-5 catalysts. The most important, K element is preferentially deposited at -OH on the surface of ZSM-5 carrier due to the electrostatic attraction (-O-K). As for the K&SO2 poisoning catalyst, SO2 preferred to be combined with the surface-deposited K (-O-K-SO2ads) according to XPS and density functional theory (DFT) results, the poisoned active sites by K would be released. The K migration behavior was induced by SO2 over K-poisoned MnSmOx@ZSM-5 catalysts, and the balance of surface redox and acidic site was regulated, like a synergistic promoter, which led to K-poisoning buffering and activity recovery. This work contributes to the understanding of the self-detoxification interaction between alkali metals (e.g., K) and SO2 on deNOx catalysts and provides a novel strategy for the adaptive use of one poisoning substance to counter another for practical NOx reduction.

Assessing health risks from bioaccessible PM2.5-bound toxic metals in Nanchang metro: Implications for metro workers and emissions control.

High concentrations of PM2.5 with enriched levels of metallic constituents could significantly affect the health and comfort of metro employees. To avoid overestimating the exposure risks, we investigated the bioaccessibility of toxic metals (TMs) bound in PM2.5 from the Nanchang metro using Gamble's solution method, and qualitatively analyzed the impact of valence state and various sources on the bioaccessibility of TMs bound to PM2.5. The results showed that the bioaccessibility of the studied TMs ranged from 2.1% to 88.1%, with As, Ba, Co and Pb being the most bioaccessible and V, Fe and Cr being the less bioaccessible. The bioaccessibility of TMs in our subway PM2.5 samples varied based on their valence and species, showing higher valence states associated with increased bioaccessibility. Vehicle traffic, secondary aerosols and wheel/rail sources were found to be significantly and positively associated with the bioaccessibility of several TMs, implying a severe potential risk from these three sources. Although both non-carcinogenic and carcinogenic risks associated with total TMs were found to be high, only As and Cr(VI) posed a considerable carcinogenic risk to metro workers based on the bioaccessible fractions and were therefore priority pollutants. In addition, potential carcinogenic risk was found to be more severe in platform than that in ticket counter. The results indicate that considerable efforts are required to control and manage PM2.5 and the associated TMs in the Nanchang subway, particularly from traffic, wheel/rail and secondary sources, to protect the health of metro staff and the public.

Divergent response and adaptation of specific leaf area to environmental change at different spatio-temporal scales jointly improve plant survival.

Specific leaf area (SLA) is one of the most important plant functional traits. It integrates multiple functions and reflects strategies of plants to obtain resources. How plants employ different strategies (e.g., through SLA) to respond to dynamic environmental conditions remains poorly understood. This study aimed to explore the spatial variation in SLA and its divergent adaptation through the lens of biogeographic patterns, evolutionary history, and short-term responses. SLA data for 5424 plant species from 76 natural communities in China were systematically measured and integrated with meta-analysis of field experiments (i.e., global warming, drought, and nitrogen addition). The mean value of SLA across all species was 21.8 m2  kg-1 , ranging from 0.9 to 110.2 m2  kg-1 . SLA differed among different ecosystems, temperature zones, vegetation types, and functional groups. Phylogeny had a weak effect on SLA, but plant species evolved toward higher SLA. Furthermore, SLA responded nonlinearly to environmental change. Unexpectedly, radiation was one of the main factors determining the spatial variation in SLA on a large scale. Conversely, short-term manipulative experiments showed that SLA increased with increased resource availability and tended to stabilize with treatment duration. However, different species exhibited varying response patterns. Overall, variation in long-term adaptation of SLA to environmental gradients and its short-term response to resource pulses jointly improve plant adaptability to a changing environment. Overall SLA-environment relationships should be emphasized as a multidimensional strategy for elucidating environmental change in future research.

Effect of renal denervation on cardiac remodelling and function in rats with chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) mimicking obstructive sleep apnea elicits divergent outcomes in the cardiovascular systems. The effect of renal denervation (RDN) on the heart during CIH remains unclear. We aimed to explore the effect of RDN on cardiac remodelling in rats exposed to CIH and to discuss the underlying mechanisms. Adult Sprague Dawley rats were divided into four groups: control, control+RDN, CIH (CIH exposure for 6 weeks, nadir of 5%-7% to peak of 21% O2, 20 cycles/h, 8 h/day) and CIH+ RDN group. Echocardiography, cardiac fibrosis, left ventricle (LV) expressions of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inflammatory factors were tested at the end of the study. Cardiac structural remodelling and dysfunction were induced by CIH and attenuated by RDN. Myocardial fibrosis was more severe in the CIH group than in the control group and improved in the CIH + RDN group. Sympathetic activity reflected by tyrosine hydroxylase (TH) expression and noradrenaline were significantly elevated after CIH but blunted by RDN. CIH downregulated LV protein expressions of Nrf2 and HO-1, which was activated by RDN. The downstream of Nrf2/HO-1, such as NQO1 and SOD expression, elevated following RDN. RDN also decreased the mRNA expression of IL-1ß and IL-6. Notably, control+RDN did not affect cardiac remodelling and Nrf2/HO-1 compared with the control. Taken together, we found that RDN exerted cardio-protective effects in a rat model of CIH involving Nrf2/HO-1 pathway and inflammation.

Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury.

OBJECTIVE: To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury. METHODS: Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O2 concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively. RESULTS: Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-ß1 and tumor necrosis factor-alpha in the aorta. CONCLUSION: SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.

Facilitating Redox Cycles of Copper Species by Pollutants in Peroxymonosulfate Activation.

The redox behavior of metal active sites determines the rate of heterogeneous catalysis in peroxymonosulfate activation. Previous reports focused on the construction of catalysts for accelerating interfacial electron transfer. In this work, a new strategy was proposed for facilitating valence cycles of Cu+/Cu2+ by using pollutants. The 2.5Cu/CeO2/PMS system was capable of achieving the efficient removal of pollutants, including tetracycline, oxytetracycline, and rhodamine B, in a wide pH working range. In the presence of tetracycline, a Cu-N bond was formed between the -NH2 group of tetracycline and the Cu site of the catalyst, showing that the coordination of Cu active sites changed to CuO4N1. The charge of CuO4N1 active sites rearranged, making it easier to obtain electrons and promote the PMS oxidation, thereby accelerating the reduction of Cu2+ to Cu+ and PMS activation. The PMS activation system showed excellent sustainability and selectivity for the removal of organic pollutants. This study provides a novel routine to promote peroxymonosulfate activation by utilizing pollutants to accelerate the redox behavior of metal species.

Editing homologous copies of an essential gene affords crop resistance against two cosmopolitan necrotrophic pathogens.

Sclerotinia sclerotiorum and Botrytis cinerea are typical necrotrophic pathogens that can attack more than 700 and 3000 plant species, respectively, and cause huge economic losses across numerous crops. In particular, the absence of resistant cultivars makes the stem rot because of S. sclerotiorum the major threat of rapeseed (Brassica napus) worldwide along with Botrytis. Previously, we identified an effector-like protein (SsSSVP1) from S. sclerotiorum and a homologue of SsSSVP1 on B. cinerea genome and found that SsSSVP1 could interact with BnQCR8 of rapeseed, a subunit of the cytochrome b-c1 complex. In this study, we found that BnQCR8 has eight homologous copies in rapeseed cultivar Westar and reduced the copy number of BnQCR8 using CRISPR/Cas9 to improve rapeseed resistance against S. sclerotiorum. Mutants with one or more copies of BnQCR8 edited showed strong resistance against S. sclerotiorum and B. cinerea. BnQCR8-edited mutants did not show significant difference from Westar in terms of respiration and agronomic traits tested, including the plant shape, flowering time, silique size, seed number, thousand seed weight and seed oil content. These traits make it possible to use these mutants directly for commercial production. Our study highlights a common gene for breeding of rapeseed to unravel the key hindrance of rapeseed production caused by S. sclerotiorum and B. cinerea. In contrast to previously established methodologies, our findings provide a novel strategy to develop crops with high resistance against multiple pathogens by editing only a single gene that encodes the common target of pathogen effectors.

Mechanism and stability investigation of a nozzle-free droplet-on-demand acoustic ejector.

This paper investigates the mechanism of a new acoustic micro-ejector using a Lamb wave transducer array, which can stably generate picoliter (pL) droplet jetting without nozzles. With eight transducers arranged as an octagon array, droplets are ejected based on the mechanism of combined acoustic pressure waves and acoustic streaming. The acoustic focusing area is designed as a line at the liquid center, which is the key factor for a large working range of liquid height. The experimental results show that the ejector can produce uniform water droplets of 22 µm diameter (5.6 pL in volume) continuously at a rate of 0.33 kHz with high ejection stability, owing to a large liquid height window and high acoustic wave frequency. By delivering precise ∼pL droplets without clogging issues, the acoustic ejector has great potential for demanding biochemical applications.

Terahertz-frequency temporal differentiator enabled by a high-Q resonator.

Terahertz (THz) fundamental "building blocks" equivalent to those used in multi-functional electronic circuits are very helpful for actual applications in THz data-processing technology and communication. Here, we theoretically and experimentally demonstrate a THz temporal differentiator based on an on-chip high-quality (Q) factor resonator. The resonator is made of low-loss high-resistivity silicon material in a monolithic, integrated platform, which is carefully designed to operate near the critical coupling region. The experiment demonstrates that the device can perform the first-order time derivative of the input signal electric field complex envelope at 214.72 GHz. Our investigation provides an effective approach for terahertz pulse re-shaping and real-time differential computing units.

Efficient Fenton-like Process for Pollutant Removal in Electron-Rich/Poor Reaction Sites Induced by Surface Oxygen Vacancy over Cobalt-Zinc Oxides.

To achieve high efficiency and low consumption for water treatment in the Fenton reaction, we use the surface oxygen vacancies (OVs) as the electron temporary residences to construct a dual-reaction-center (RDC) Fenton-like catalyst with abundant surface electron-rich/poor areas consisting of OV-rich Co-ZnO microparticles (OV-CoZnO MPs). The lattice-doping of Co into ZnO wurtzite results in the formation of OVs with unpaired electrons (electron-rich OVs) and electron-deficient Co3+ sites according to the structural and electronic characterizations. Both experimental and theoretical calculations prove that the electron-rich OVs are responsible for the capture and reduction of H2O2 to generate hydroxyl radicals, which quickly degrades pollutants, while a large amount of pollutants are adsorbed at the electron-deficient Co3+ sites and act as electron donors for the system, accompanied by their own oxidative degradation. The electrons obtained from the pollutants in the electron-deficient sites are transferred to the OVs through the internal bond bridge to achieve the balance of electron gain/loss. Through this process, pollutants are efficiently converted and degraded by multiple pathways in a wide range of pH (4.5-9.5). The reaction rate of the OV-CoZnO MPs/H2O2 system is increased by ∼17 times compared with the non-DRC system. This discovery provides a sustainable strategy for pollutant utilization, which shows new implications for solving the troublesome issues of the Fenton reaction and for developing novel environmental remediation technologies.

The enhanced expression of estrogen-related receptor α in human bladder cancer tissues and the effects of estrogen-related receptor α knockdown on bladder cancer cells.

Estrogen-related receptor α (ERRα) belongs to the superfamily of nuclear orphan receptors. However, the role of ERRα in bladder cancer remains unknown. This study examined the expression of ERRα in bladder cancer tissues and explored the molecular mechanisms of ERRα in bladder cancer progression. The expression of ERRα in bladder cancer tissues from 61 patients was determined by immunohistochemistry. We performed quantitative real-time polymerase chain reaction assay to detect the gene expression levels and carried out Western blot assay to measure protein levels. In vitro functional assays, including colony formation, Cell Counting Kit-8, Transwell invasion, and migration assays, were performed to detect bladder cancer cell growth, proliferation, invasion, and migration, respectively. Flow cytometry was used to determine the cell apoptotic rate of bladder cancer cells. Among the 61 detected bladder cancer tissues, 39 bladder cancer tissues showed positive ERRα immunoreactivity. Higher ERRα immunoreactivity score was significantly associated with TNM stage, tumor grade, distant metastasis, and poor survival in patients with bladder cancer. Univariate and multivariate analyses showed that ERRα immunoreactivity was an independent prognostic factor for overall survival in patients with bladder cancer. ERRα was found to be upregulated in bladder cancer cell lines, and knockdown of ERRα suppressed bladder cancer cell growth, proliferation, invasion, and migration; promoted bladder cancer cell apoptosis; and inhibited the epithelial-mesenchymal transition of bladder cancer cells. On the other hand, bladder cancer cell proliferation, invasion, and migration were significantly enhanced after cells were transfected with an ERRα-overexpressing vector. In vivo tumor growth and metastasis assays showed that ERRα knockdown resulted in remarkable inhibition of tumor growth and tumor metastasis in nude mice. Collectively, our results suggest that the enhanced expression of ERRα may play a key role in the development and progression of bladder cancer and ERRα may serve as an important prognostic factor for bladder cancer.

cDNA cloning, characterization, and expression analysis of the Rac1 and Rac2 genes from Cynoglossus semilaevis.

Rac1 and Rac2, belonging to the small Rho GTPase family, play an important role during the immune responses. In this study, a Rac1 homolog (CsRac1) and a Rac2 homolog (CsRac2) were cloned from the Cynoglossus semilaevis. The full-length of CsRac1 and CsRac2 cDNA was 1219 bp and 1047 bp, respectively. Both CsRac1 and CsRac2 contain a 579 bp open reading frame (ORF) which encoding a 192 amino acids putative protein. The predicted molecular weight of CsRac1 and CsRac2 was 21.41 kDa and 21.35 kDa, and their theoretical pI was 8.50 and 7.91, respectively. Sequence analysis showed that the conserved RHO domain was detected both from amino acid of CsRac1 and CsRac2. Homologous analysis showed that CsRac1 and CsRac2 share high conservation with other counterparts from different species. The CsRac1 and CsRac2 transcript showed wide tissue distribution, in which CsRac1 and CsRac2 exhibit the highest expression level in liver and gill, respectively. The expression level of CsRac1 and CsRac2 fluctuated in the liver and gill tissues at different time points after challenged by Vibrio harveyi. Specifically, CsRac1 and CsRac2 were significantly up-regulated at 48 h and 96 h post injection. Moreover, the knocking down of CsRac1 and CsRac2 in cell line (TSHKC) reduced the expression of CsPAK1, CsIL1-ß and CsTNF-α. The present data suggests that CsRac1 and CsRac2 might play important roles in the innate immunity of half-smooth tongue sole.

Cloning, expression prolife, and immune characterization of a novel stat family member (stat5bl) in Chinese tongue sole (Cynoglossus semilaevis).

STAT plays important roles in innate immunity during JAK/STAT signaling pathway, and STAT5 is particularly focused due to the existence of duplicated forms in fish and mammal. In Chinese tongue sole, stat5bl was suggested to be a candidate related to Vibrio harveyi resistance based on previous QTL screening. In this study, the full length of stat5bl cDNA was cloned and its expression patterns were analyzed. stat5bl was predominantly expressed in immune tissues, where the highest level was observed in liver, followed by skin and gill. Time course expression patterns were examined in six tissues (liver, skin, gill, kidney, intestine, spleen) after V. harveyi infection. stat5bl could be up-regulated by V. harveyi infection in all tissues except liver, despite the timepoints of peak were different. In contrast, stat5bl was significantly downregulated in liver. To elucidate the role of stat5bl in liver, in vitro RNAi were performed using primary liver cell culture. Knockdown of stat5bl could regulate the expression of genes closely related to JAK/STAT pathway. This study would enlarge our understanding of stat5bl in fish immunity.

Programmable multi-DNA release from multilayered polyelectrolytes using gigahertz nano-electromechanical resonator.

BACKGROUND: Controllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. To overcome the restrictions on the materials and environment, a novel and versatile DNA release method using a nano-electromechanical (NEMS) hypersonic resonator of gigahertz (GHz) frequency is developed. RESULTS: The micro-vortexes excited by ultra-high frequency acoustic wave can generate tunable shear stress at solid-liquid interface, thereby disrupting molecular interactions in immobilized multilayered polyelectrolyte thin films and releasing embedded DNA strands in a controlled fashion. Both finite element model analysis and experiment results verify the feasibility of this method. The release rate and released amount are confirmed to be well tuned. Owing to the different forces generated at different depth of the films, release of two types of DNA molecules with different velocities is achieved, which further explores its application in combined gene therapy. CONCLUSIONS: Our research confirmed that this novel platform based on a nano-electromechanical hypersonic resonator works well for controllable single and multi-DNA release. In addition, the unique features of this resonator such as miniaturization and batch manufacturing open its possibility to be developed into a high-throughput, implantable and site targeting DNA release and delivery system.

Controlled and Tunable Loading and Release of Vesicles by Using Gigahertz Acoustics.

Controllable exchange of molecules between the interior and the external environment of vesicles is critical in drug delivery and micro/nano-reactors. While many approaches exist to trigger release from vesicles, controlled loading remains a challenge. Herein, we show that gigahertz acoustic streaming generated by a nanoelectromechanical resonator can control the loading and release of cargo into and from vesicles. Polymer-shelled vesicles showed loading and release of molecules both in solution and on a solid substrate. We observed deformation of individual giant unilamellar vesicles and propose that the shear stress generated by gigahertz acoustic streaming induces the formation of transient nanopores, with diameters on the order of 100 nm, in the vesicle membranes. This provides a non-invasive method to control material exchange across membranes of different types of vesicles, which could allow site-specific release of therapeutics and controlled loading into cells, as well as tunable microreactors.

Cardiac resynchronization therapy improves left ventricular remodeling and function compared with right ventricular pacing in patients with atrioventricular block.

Right ventricular pacing (RVP) exerts a detrimental effect on left ventricular (LV) remodeling. In patients with atrioventricular block (AVB) that require ventricular pacing, the effect of biventricular pacing (BiVP) versus RVP on LV remodeling and function has not been comprehensively assessed in a meta-analysis. Electric databases MEDLINE and Cochrane Library were retrieved for randomized controlled trials (RCT) comparing RVP and BiVP in patients with AVB. Data on left ventricular ejection fraction (LVEF) and LV volumes were analyzed, stratified by different time points. Eleven RCTs were included in the final analysis. There was a significant reduction of LV end-systolic volume in BiVP compared with RVP, at 3, 6, 12, and 24 months follow-up (P < 0.05 for all). BiVP was associated with a decreased LV end-diastolic volume in comparison to RVP at 3, 6, and 12 months. Compared with RVP, BiVP had a higher LVEF at all follow-up visits, with mean difference of 5.91, 3.29, 3.9, 6.66, and 8.69% at 3, 6, 12, 24, and beyond 24 months follow-up, respectively. The results were not significantly changed in sensitivity analysis after removal of studies with mean baseline LVEF < 50% or excluding studies with ablation-induced AVB. In patients with AVB and bradycardia that require ventricular pacing, BiVP is superior to RVP in improving LV remodeling and function.

Clinical outcomes with biventricular versus right ventricular pacing in patients with atrioventricular conduction defects.

There have been increasing concerns about the unexpected effects of right ventricular (RV) pacing. We aimed to systematically evaluate the effect of biventricular (BiV) versus RV pacing on clinical events in patients with impaired AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies comparing BiV pacing with RV pacing in patients with AV block, through April 2017. We selected randomized controlled trials (RCTs) reporting data on mortality, hospitalization for heart failure (HF), and/or 6-min walk distance (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that BiV pacing was associated with a significantly reduced all-cause mortality in contrast to RV pacing (risk ratio (RR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, I2 = 9.6%). BiV pacing, compared with RV pacing, significantly reduced the rate of HF hospitalization (RR = 0.74, 95% CI 0.59 to 0.93, I2 = 10.1%). Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV pacing still had a lower mortality and non-significant reduced HF hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow-up (mean difference = 4.99 m, 95% CI - 11.34 to 21.33 m, I2 = 0%). Meta-regression analysis showed that the effect size of all-cause mortality or HF hospitalization was not significantly associated with mean LVEF value at baseline. In patients with impaired AV conduction that need frequent ventricular pacing, BiV pacing was associated with reduced mortality and hospitalization for HF, compared with traditional RV pacing mode.

Hypersonic Poration: A New Versatile Cell Poration Method to Enhance Cellular Uptake Using a Piezoelectric Nano-Electromechanical Device.

Efficient delivery of genes and therapeutic agents to the interior of the cell is critical for modern biotechnology. Herein, a new type of chemical-free cell poration method-hypersonic poration-is developed to improve the cellular uptake, especially the nucleus uptake. The hypersound (≈GHz) is generated by a designed piezoelectric nano-electromechanical resonator, which directly induces normal/shear stress and "molecular bombardment" effects on the bilayer membranes, and creates reversible temporal nanopores improving the membrane permeability. Both theory analysis and cellular uptake experiments of exogenous compounds prove the high delivery efficiency of hypersonic poration. Since target molecules in cells are accumulated with the treatment, the delivered amount can be controlled by tuning the treatment time. Furthermore, owing to the intrinsic miniature of the resonator, localized drug delivery at a confined spatial location and tunable arrays of the resonators that are compatible with multiwell plate can be achieved. The hypersonic poration method shows great delivery efficacy combined with advantage of scalability, tunable throughput, and simplification in operation and provides a potentially powerful strategy in the field of molecule delivery, cell transfection, and gene therapy.