The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study.

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. Design: A retrospective cohort study. Setting: Tertiary-care academic medical center. Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

Comprehensive Functional Analysis of the bZIP Family in Bletilla striata Reveals That BsbZIP13 Could Respond to Multiple Abiotic Stresses.

Basic leucine zipper (bZIP) transcription factors (TFs) are one of the largest families involved in plant physiological processes such as biotic and abiotic responses, growth, and development, etc. In this study, 66 members of the bZIP family were identified in Bletilla striata, which were divided into 10 groups based on their phylogenetic relationships with AtbZIPs. A structural analysis of BsbZIPs revealed significant intron-exon differences among BsbZIPs. A total of 63 bZIP genes were distributed across 16 chromosomes in B. striata. The tissue-specific and germination stage expression patterns of BsbZIPs were based on RNA-seq. Stress-responsive expression analysis revealed that partial BsbZIPs were highly expressed under low temperatures, wounding, oxidative stress, and GA treatments. Furthermore, subcellular localization studies indicated that BsbZIP13 was localized in the nucleus. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays suggested that BsbZIP13 could interact with multiple BsSnRK2s. The results of this study provide insightful data regarding bZIP TF as one of the stress response regulators in B. striata, while providing a theoretical basis for transgenic and functional studies of the bZIP gene family in B. striata.

[Distribution, Sources, and Risk Assessment of Microplastics in Surface Sediments of Yellow River Delta Wetland].

Estuarine habitats are a critical zone of the Earth with strong land-sea interactions, that are strongly influenced by human activities. Microplastics (MPs) pollution in the Yellow River Delta (YRD) wetland, a typical young warm-temperate estuarine wetland, has not been comprehensively studied. The morphology, abundance, particle size, and polymer composition of MPs in the surface sediments of the YRD wetland were determined, and the pollution status and ecological risk in the study area were evaluated using the pollution load index (PLI) and potential pollution risk index (PRI). The results showed that the abundance of MPs in the YRD wetland was 20-520 n·kg-1, with a median value of 150 n·kg-1. The MPs were primarily fibers in shape and black in color, with particle size over 1 mm. The polymer components were primarily rayon, polyethylene, polyester, and polyethylene terephthalate. The PLI and PRI values of the MPs in the area were between 0.04-0.96 and 0.00-171.60, respectively, indicating that the pollution of MPs in the YRD wetland was at a slightly polluted level with low ecological risk.

Spatial distribution and sources of heavy metals in the sediment and soils of the Yancheng coastal ecosystem and associated ecological risks.

Studies of heavy metal pollution are essential for the protection of coastal environments. In this study, positive matrix factorization (PMF) and a GeoDetector model were used to evaluate the sources of heavy metal contamination and associated ecological risks along the Yancheng Coastal Wetland. The distribution of heavy metals was shown to be greatly affected by clay content, except for Cr in shoal. Components from 6.5 to 9φ have the strongest ability to absorb heavy metals, where the effects of Cd and Zn sequestration in the wetlands were most apparent. The abilities of various wetland environments to sequester heavy metals were shown to be Spartina alterniflora wetland > woodland > Phragmites australis wetland > aquaculture pond > shoal > paddy > meadow > dry land. The sources of the heavy metals included parent soil material (59%), agriculture (15%), and industrial pollutants (26%). According to the single-factor pollution index, there was no evidence of pollution except Cr and Pb. In general, the heavy metal pollution was insignificant. The order of pollution loading index was shoal > paddy field > dry land > Spartina Alterniflora wetland > aquaculture ponds > woodland > meadow > Phragmites australis wetland. The ecological harm of heavy metal exposure was slight except for Cd and Hg, where vehicle emissions appeared to be the main cause of heavy metal pollution.

Hydrochemical evolution processes of multiple-water quality interfaces (fresh/saline water, saline water/brine) on muddy coast under pumping conditions.

A thorough understanding of the evolution of coastal brine-bearing groundwater systems under the influence of human activities contributes to the sustainable use of coastal groundwater resources. Therefore, this study comprehensively investigated the processes associated with hydrochemical changes in groundwater during brine exploitation based on long-term monitoring data. The dataset comprised 102 samples (including groundwater, seawater, rain and river samples) collected from 1966 to 2021 to capture the hydrochemical variability. Significant changes in the brine water table and concentration between the pre-overexploitation period (1965-2000) and the exploitation period (2000-2021) are observed. From the relationship between stable isotope (δ18O and δ2H) values and Cl- contents, shallow saline water (SSW) near the drawdown cone (with δ18O and δ2H values of -4.66 ‰ ~ -3.57 ‰ and - 42.1 ‰ ~ -32.8 ‰, respectively) is similar geochemically to the brine inside the drawdown cone (with values of -4.30 ‰ ~ -3.10 ‰ and - 39.0 ‰ ~ -32.3 ‰, respectively), indicating that the SSW has a recharge effect on the underground brine. The delta values of major cations were calculated to analyze the hydrochemical processes at different water quality interfaces (saline/freshwater interface, salinewater/brine interface). The results demonstrated that the SSW and deep saline water (DSW) at the offshore brine/saline water interface undergo seawater intrusion, where SSW undergoes a salinization process with cation exchange (Na+ is exchanged for Ca2+ and Mg2+ in clay), while DSW undergoes a freshening process. The SSW at the saline/freshwater interface is affected by freshwater pumping, and the DSW undergoes a salinization process influenced by brine intrusion presenting the common salinization process with cation exchange. The hydrochemical model shows that the brine concentration recovered during the restricted exploitation stage due to the dissolution of gypsum and halite. If no measures are taken to restrict exploitation, then brine will eventually be replaced by saline water.

Geochemical characteristics of heavy metals in surface sediments of the Bohai Strait, China.

The heavy metal (Cr, Cu, Ni, Pb, and Zn) content and particle size of surface sediment samples taken from 123 sites in the Bohai Strait of China were analyzed. All five heavy metals showed a similar distribution in the Bohai Strait, with lower concentrations in the middle and higher concentrations at the sides of the strait. The amount of heavy metals was lowest in the Laotieshan Channel due to the rapid current in this channel. According to our calculated values of the pollution index (Pi), only 1.6 % of the sample sites were polluted by Cr and Cu. The calculated geo-accumulation index (Igeo) values showed that few of the sites were polluted by heavy metals. The level of Pb was controlled by both terrigenous inputs and clay adsorption, while the levels of the other heavy metals (Cr, Cu, Ni, and Zn) were mainly controlled by terrigenous inputs.

Comparison of weight loss and adverse events of obesity drugs in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: The global incidence of childhood obesity is increasing. Currently, there are only few established drugs for treating adolescent obesity. Randomized clinical trials (RCTs) comparing pharmacological interventions in children with obesity are scarce; therefore, we aimed to analyze the relative efficacy and adverse reactions of these drugs and compare the effects of each drug on body mass index (BMI). RESEARCH DESIGN AND METHODS: This meta-analysis focused on the slimming effect, safety, and correlation of metformin, orlistat, exenatide, liraglutide, and topiramate in children with obesity. Several international databases were searched and clinical trials on the treatment of obesity in children in which the drug was administered for ≥ 6 months were included. Changes in BMI before and after treatment were analyzed using a Bayes framework, and the surface under the cumulative ranking was calculated. RESULTS: Of 2102 relevant articles retrieved, 21 RCTs were included in the study. Compared to other drugs, liraglutide reduced BMI the most in children with obesity. However, it was most associated with drug withdrawal due to adverse events while topiramate was least. CONCLUSIONS: Liraglutide had a higher probability of achieving clinically significant weight loss compared with other drugs while topiramate was superior in safety.

UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through TRPA1 Channels.

Purpose: Ultraviolet radiation (UVR) enhances skin pigmentation, which involves the production of melanin by melanocytes and subsequent transfer to keratinocytes. In the epidermis, keratinocyte phagocytosis plays a pivotal role in the process of melanosome transfer to protect DNA of epidermal cells against damage from UVR. Previous research suggested that transient receptor potential channels ankyrin 1 (TRPA1) was required for UVR-induced early melanin synthesis in melanocytes. Currently, there is no evidence that supports the detailed mechanism of TRPA1 for UVR-induced phagocytosis by keratinocytes. Here, we investigated the effect and the possible mechanisms of TRPA1 on keratinocyte phagocytosis and skin pigmentation after UVR exposure. Methods: Flow cytometry was applied to investigate the effect of TRPA1 on intracellular calcium concentration ([Ca2+]ic) and fluorescent microspheres uptake was carried out to analyze phagocytosis in HaCaT cells (human immortalized keratinocytes). Western blotting was applied to measure the protein expression of calcium/calmodulin-dependent protein kinase II (CaMKII), phosphorylated CaMKII and ß-catenin after UVA/UVB exposure. Masson-Fontana staining was applied to observe the effect of XAV-939 (decreasing the expression of ß-catenin) on UVB-induced skin pigmentation in guinea pigs. Results: TRPA1 channels activated by UVR increased the [ca2+]ic and phosphorylation of CaMKII in HaCaT cells. The UVR-induced phagocytosis was regulated by TRPA1 in HaCaT cells. TRPA1 promoted the protein expression of ß-catenin after UVR exposure in HaCaT cells. XAV-939, inhibiting ß-catenin expression, decreased the UVB-induced skin pigmentation on in vivo guinea pig models. Conclusion: Taken together, TRPA1 activated by UVR led to the increase of intracellular calcium, which promoted the phosphorylation of CaMKII, enhancing keratinocyte phagocytosis. Moreover, TRPA1 regulated the protein expression of ß-catenin to exert a lightening effect on skin pigmentation. Our findings suggest that TRPA1 may be a potential therapeutic target for UVR-induced skin pigmentary diseases.

TRPA1 promotes melanosome phagocytosis in keratinocytes via PAR-2/CYLD axis.

BACKGROUND: Keratinocytes are recipients of melanosomes. Although the chemical basis of melanogenesis is well documented, the molecular mechanism of melanosome transfer must be elucidated. TRPA1 is a member of the transient receptor potential A subfamily. Previous studies have shown that inhibition of TRPA1 activity reduces melanin synthesis in human epidermal melanocytes; however, the mechanism remains unknown. OBJECTIVE: This study aimed to investigate the roles and mechanism(s) of action of TRPA1 in keratinocytes. METHODS: The correlation between TRPA1 expression levels and the ability of keratinocytes to phagocytize melanosomes was examined using melanin silver staining. TRPA1 depleted human epidermal keratinocytes and keratinocyte cell lines HaCaT were established using adenovirus-expressing shRNAs against TRPA1. The effects of TRPA1 on keratinocytes and HaCaT cells were determined using cell-based analyses, including light stimulation, calcium imaging, melanin phagocytosis, immunoblotting, and co-immunoprecipitation assays. The degree of epidermal pigmentation was determined in a guinea pig model. RESULTS: TRPA1 mediated the phagocytic activity of keratinocytes. TRPA1 knockdown markedly suppressed melanosome transport to keratinocytes. Mechanistically, TRPA1 was required for PAR-2-induced melanosome phagocytosis in keratinocytes. Furthermore, TRPA1 activation indirectly stabilized microtubules by promoting the competitive binding of CYLD and acetylated α-tubulin. In addition, bortezomib (PS-341), a proteasome inhibitor, increased TRPA1 and CYLD expression and promoted phagocytic activity both in vitro and in vivo. CONCLUSIONS: Our findings firstly suggest that TRPA1 promotes melanosome transport in keratinocytes and reveal that TRPA1 is a regulator of PAR-2 activation and microtubule stability via the PAR-2/CYLD axis.

Sensitive and Enzyme-Free Pathogenic Bacteria Detection Through Self-Circulation of Molecular Beacon.

This research exhibits the design of a feasible, enzyme-free and sensitive fluorescent sensing assay for the detection of Staphylococcus aureus (S. aureus), using self-circulation of molecular beacons. With protein A on S. aureus as identifying target, the capture probe binds on the surface of S. aureus based on interaction between its aptamer section and protein A. Recognition of protein A by aptamer section in capture probe leads to allosterism of capture probe, exposing initiator section to activate the following self-circulation. After multiple circulation-based signal amplification, the method exhibits a favorable detection sensitivity and shows a promising prospect for the keratitis-related pathogenic bacteria detection. The highlights of the sensing assay are as follows: (i) capture probe is designed with aptamer section which endows the method a high selectivity; (ii) signal of bacteria is converted to nucleic acid signal after recognition of target bacteria by capture probe; and (iii) high sensitivity of method is derived from the self-circulation process. Therefore, we believe that the strategy can provide a useful platform for target bacteria detection and thus contribute to the diagnosis of infectious diseases.

Expression of CDK13 Was Associated with Prognosis and Expression of HIF-1α and beclin1 in Breast Cancer Patients.

OBJECTIVE: To investigate role and clinical significance of CDK13 in breast cancer patients. METHODS: A total of 189 cases of breast cancer were enrolled during March 2013 to March 2015. Immunohistochemistry (IHC) was used for measurement of CDK13, HIF-1α and beclin1. Clinical characteristics of age, BMI, TNM stage, pathological types, and tumor diameter, were recorded. Patients' 5-year overall survival and recurrence were followed up. All patients were followed up for 5 years or to the last follow-up. RESULTS: The expression levels of CDK13 and HIF-1αin breast cancer tissues were up-regulated and beclin1 was down-regulated than in the paracancerous non-tumor tissues. CDK13 was positively correlated with HIF-1α and negatively correlated with beclin1 in breast cancer tissues. The patients with higher expression of CDK13 showed significantly higher rates of TNM III-IV, higher rates of lymph node metastasis, distant metastasis and larger tumor size. The mortality and recurrence rates were higher in high expression CDK13 patients than in low CDK13 expression patients, however with no significant difference. K-M curve showed patients with higher CDK13 showed lower 5-year overall survival and lower disease-free survival time, however with no significant difference. CONCLUSION: CDK13 was overexpressed in breast cancer tissues, and patients with higher CDK13 had poorer clinical outcomes. Further studies are still needed to reveal the clinical significance of CDK13 in breast cancer.

Performance of MoS2/Zr Composite Coatings at Different Deposition Temperatures.

The properties of the MoS2/Zr coatings can be significantly affected by the deposition temperature. In this study, the MoS2/Zr composite coatings were fabricated on the cemented carbide surface, utilizing the duplex deposition technology at various deposition temperatures. The effects of deposition temperature on the mechanical and friction properties of the MoS2/Zr coatings were systematically studied. Results exhibited that as the deposition temperature increased, the adhesion force increased first and then decreased, and the coating thickness and micro-hardness gradually increased. Dry sliding tests against a hardened steel ring showed that the tribological behaviors and wear mechanisms of the MoS2/Zr coatings varied with deposition temperature, which were due to the changing mechanical properties of coatings caused by the temperature. The coatings deposited at a temperature of 180 °C and 200 °C possessed preferable comprehensive mechanical and tribological properties.

Direct Observation of Oxygen Evolution and Surface Restructuring on Mn2O3 Nanocatalysts Using In Situ and Ex Situ Transmission Electron Microscopy.

Direct observation of oxygen evolution reaction (OER) on catalyst surface may significantly advance the mechanistic understanding of OER catalysis. Here, we report the first real-time nanoscale observation of chemical OER on Mn2O3 nanocatalyst surface using an in situ liquid holder in a transmission electron microscope (TEM). The oxygen evolution process can be directly visualized from the development of oxygen nanobubbles around nanocatalysts. The high spatial and temporal resolution further enables us to unravel the real-time formation of a surface layer on Mn2O3, whose thickness oscillation reflects a partially reversible surface restructuring relevant to OER catalysis. Ex situ atomic-resolution TEM on the residual surface layer after OER reveals its amorphous nature with reduced Mn valence and oxygen coordination. Besides shedding light on the dynamic OER catalysis, our results also demonstrate a powerful strategy combining in situ and ex situ TEM for investigating various chemical reaction mechanisms in liquid.

Graded bulk-heterojunction enables 17% binary organic solar cells via nonhalogenated open air coating.

Graded bulk-heterojunction (G-BHJ) with well-defined vertical phase separation has potential to surpass classical BHJ in organic solar cells (OSCs). In this work, an effective G-BHJ strategy via nonhalogenated solvent sequential deposition is demonstrated using nonfullerene acceptor (NFA) OSCs. Spin-coated G-BHJ OSCs deliver an outstanding 17.48% power conversion efficiency (PCE). Depth-profiling X-ray photoelectron spectroscopy (DP-XPS) and angle-dependent grazing incidence X-ray diffraction (GI-XRD) techniques enable the visualization of polymer/NFA composition and crystallinity gradient distributions, which benefit charge transport, and enable outstanding thick OSC PCEs (16.25% for 300 nm, 14.37% for 500 nm), which are among the highest reported. Moreover, the nonhalogenated solvent enabled G-BHJ OSC via open-air blade coating and achieved a record 16.77% PCE. The blade-coated G-BHJ has drastically different D-A crystallization kinetics, which suppresses the excessive aggregation induced unfavorable phase separation in BHJ. All these make G-BHJ a feasible and promising strategy towards highly efficient, eco- and manufacture friendly OSCs.

Nanostructure-Mediated Phase Evolution in Lithiation/Delithiation of Co3O4.

Nanostructured transition-metal oxides have been under intensive investigation for their tantalizing potential as anodes of next-generation lithium-ion batteries (LIBs). However, the exact mechanism for nanostructures to influence the LIB performance remains largely elusive. In this work, we discover the nanostructure-mediated lithiation mechanism in Co3O4 anodes using ex situ transmission electron microscopy (TEM) and X-ray diffractometry: while Co3O4 nanosheets exhibit a typical two-step conversion reaction (from Co3O4 to CoO and then to Co0), Co3O4 nanoarrays can go through a direct conversion from Co3O4 to Co0 at a high discharge rate. Such nanostructure-dependent lithiation can be rationalized by the slow lithiation kinetics intrinsic to Co3O4 nanoarrays, which at a high discharge rate may cause local accumulation of lithium to initiate a one-step Co3O4-to-Co0 conversion. Combined with the larger volume change observed in Co3O4 nanoarrays, the slow lithiation kinetics can lead to inhomogeneous expansion with large stress developed at the reaction front, which can eventually cause structure failure and irreversible capacity loss, as explicitly observed by in situ TEM as well as galvanostatic discharge-charge measurement. Our observation resolves the nanostructure-dependent lithiation mechanism of Co3O4 and provides important insights into the interplay among lithiation kinetics, phase evolution, and lithium-storage performance, which can be translated into electrode design strategies for next-generation LIBs.

Pollen distribution and transportation patterns in surface sediments of Liaodong Bay, China.

Understanding pollen transport pathways and dispersal mechanism from the land to sea is a prerequisite for marine palynological study. Palynological analysis of 164 surface sediment samples in Liaodong Bay, and 39 analogous surface alluvium samples from its five inflowing rivers, identifies the distribution patterns, pathways and possible sources of pollen and spores. The results show that pollen and spore assemblages in surface sediments are well correlated to regional vegetation distribution, and the variations of pollen assemblage in different parts of Liaodong Bay reflected local vegetation changes along the coast. High pollen concentrations are mainly distributed in the estuaries of inflowing rivers, coastal waters and sea muddy areas. The pollen assemblage characteristics of alluvial samples are similar to those from coastal waters with water depths <8.5 m. Samples from the alluvium and surface sediments of coastal waters were dominated by herbaceous pollen taxa including Artemisia, Amaranthaceae, Poaceae, Cyperaceae and Typha. Herbaceous pollen percentages and concentrations decreased as the water depth increased, indicating that pollen and spores in the coastal waters of Liaodong Bay are mainly carried by the inflowing rivers. However, pollen assemblages for samples with water depth >8.5 m are significantly different from those of the alluvium. In samples taken below a depth of 8.5 m, the arboreal pollen is dominated by airborne Pinus, and there is a high number of the waterborne Selaginella fern spores, both of which are sourced from a wider region. In the Liaodong Bay, both wind and ocean current transportation determines the pollen distribution patterns in deeper waters, while fluvial and longshore current transportation determines the pollen assemblages found in shallow waters. The dispersal characteristics of pollen assemblages between the land and the sea in Liaodong Bay provide a theoretical basis for the interpretation of fossil pollen assemblages and past sea level changes.

Induced transparency by interference or polarization.

Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow light and optical/quantum storage. Here we study the polarization effects in various optical EIT systems. We find that a polarization mismatch between whispering gallery modes in two indirectly coupled resonators can induce a narrow transparency window in the transmission spectrum resembling the EIT lineshape. However, such polarization-induced transparency (PIT) is distinct from EIT: It originates from strong polarization rotation effects and shows a unidirectional feature. The coexistence of PIT and EIT provides additional routes for the manipulation of light flow in optical resonator systems.

Non-catecholamine vasopressors in the treatment of adult patients with septic shock-evidence from meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Norepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients. METHODS: We conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. RESULTS: Twenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86-0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70-1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, - 0.43; 95% CI - 0.66 - - 0.19; P < 0.001), serum creatinine (- 0.15; 95% CI - 0.29 - - 0.01; P = 0.04), and the length of mechanical ventilation (MV) (- 0.19; 95% CI - 0.31 - - 0.07; P < 0.01, but there was no significant difference in other parameters. CONCLUSIONS: Current pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.

Retraction Note to: Associations of IL-8 gene polymorphisms and IL-8 levels with predisposition to age-related macular degeneration: a meta-analysis.

The authors have retracted this article.

PRRSV Vaccine Strain-Induced Secretion of Extracellular ISG15 Stimulates Porcine Alveolar Macrophage Antiviral Response against PRRSV.

Porcine reproductive and respiratory syndrome virus (PRRSV) has disrupted the global swine industry since the 1980s. PRRSV-host interactions are largely still unknown but may involve host ISG15 protein. In this study, we developed a monoclonal antibody (Mab-3D5E6) specific for swine ISG15 (sISG15) by immunizing mice with recombinant sISG15. A sandwich enzyme-linked immunosorbent assay (ELISA) incorporating this sISG15-specific Mab was developed to detect sISG15 and provided a lower limit of sISG15 detection of 200 pg/mL. ELISA results demonstrated that infection of porcine alveolar macrophages (PAMs) with low-virulence or attenuated PRRSV vaccine strains induced intracellular ISG15 expression that was independent of type I IFN production, while PAMs infection with a PRRSV vaccine strain promoted extracellular ISG15 secretion from infected PAMs. Conversely, the addition of recombinant sISG15 to PAMs mimicked natural extracellular ISG15 effects whereby sISG15 functioned as a cytokine by activating PAMs. Once activated, PAMs could inhibit PRRSV replication and resist infection with PRRSV vaccine strain TJM. In summary, a sandwich ELISA incorporating homemade anti-ISG15 Mab detected ISG15 secretion induced by PAMs infection with a PRRSV vaccine strain. Recombinant ISG15 added to cells exhibited cytokine-like activity that stimulated PAMs to assume an anti-viral state that enabled them to inhibit PRRSV replication and resist viral infection.