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To compare the efficacy of different treatments for posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV) by using direct and indirect evidence from existing randomized data.Randomized case-control studies that compared the efficacy of various nonsurgical treatments in PC-BPPV patients at 1 week and 1 month of follow-up were comprehensively screened. Bayesian network meta-analysis was performed to evaluate direct and indirect treatment comparisons. We further conducted subgroup pairwise meta-analysis to explore the inconsistency between comparisons of the Epley versus a sham maneuver and the Epley versus the Semont maneuver.A total of 41 parallel, randomized controlled studies were included. The Epley with vestibular rehabilitation (EVR), Epley, Semont and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test at 1 week of follow-up (odds ratios [ORs]: 11.41-23.8, 95% credible interval [CrI]: excluding null), among which EVR showed the best efficacy (the surface area under the cumulative ranking curves [SUCRA] = 77.5%). However, at 1 month of follow-up, only the Semont (rank first, SUCRA = 76.1%) and Epley maneuvers (rank second, SUCRA = 65.3%) were effective in eliminating nystagmus during a Dix-Hallpike test. In the pairwise subgroup meta-analysis, for patients younger than 55 years of age, the efficacy of the Epley maneuver was comparable to that of the Semont maneuver [rate ratio (RR): 0.99, 95% confidence interval (CI): 0.93-1.05]; for patients with a longer duration before treatment, the effect of the Epley maneuver was equivalent to that of a sham maneuver (RR: 1.07, 95% CI: 0.90-1.29).Among the 12 types of PC-BPPV treatments, the Epley, Semont, EVR, and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test for PC-BPPV at 1 week of follow-up, whereas only the Epley and Semont maneuvers were effective at 1 month of follow-up. The duration before treatments and the age of patients might contribute to the efficacy of treatments.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated CD8+exhausted T cells (Tex) in HNSCC. We performed cell level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.Graphic abstract

SummaryPreformed-particle-gel (PPG) treatments have been successfully used in injection wells to reduce excessive water production from high-temperature, high-salinity fractured reservoirs. However, PPG itself cannot be used in fractured producers because it tends to wash out after the wells resume production. Therefore, we proposed to combine curable resin-coated particles (CRPs) with PPG to control water production from fractured producers. In this paper, millimeter-sized tubes and fractured carbonate cores were designed to comprehensively investigate water-plugging behaviors of the combined system under the conditions of various fracture parameters and PPG/CRP sizes. Particular attention was given to control the PPG washout after production was resumed. The results showed the cured CRPs could generate immobile packs in fractures and dramatically mitigate the PPG washout. The small size of the CRPs and the small ratio of CRP size to tube diameter contributed low permeability and homogeneity to CRP packs. Meanwhile, the less-permeable and more-homogeneous CRP pack, as well as the larger-sized PPGs, contributed to a higher PPG breakthrough pressure gradient. Moreover, some of the PPG particles blocked in the CRP packs could be released through high-speed brine injection from producers, which indicated the recoverability of the water plugging. This study provides a promising approach to reduce the high-water-cut problem in fractured producers.

Foam has been applied in enhanced oil recovery (EOR) for more than sixty years. The surfactant-stabilized N2/CO2 foams are two of the most widely used foams in foam EOR processes, and numerous oil reservoirs could potentially benefit from them. This paper comprehensively reviews the development of these foams over the past decade. We focused on the promising surfactant formulas and their corresponding mechanisms under different reservoir conditions, especially harsh conditions. The most recent studies have shown that low interfacial tension foaming surfactants are efficient in fractured/tight reservoirs, while CO2-switchable surfactants are well suited to CO2 foam in carbonate reservoirs with high temperatures. Pure surfactants and mixed surfactants that combine anions and cations contain superior foam properties. The surfactant aggregates, such as vesicles and wormlike micelles, could distinctly enhance the foam stability. However, the adsorption of the mixed surfactants on reservoir rocks and the temperature sensitivity of the complex structures should be given particular consideration. The phase behaviors involved in foam EOR processes are vital and much more complicated than those in other EOR processes. Thus, a better knowledge of the phase behaviors could further improve foam EOR performance. The results of this paper provide clues to N2/CO2 foam EOR design and also promote the development of harsh reservoirs.

Preformed particle gel (PPG) treatment has been well-recognized as an efficient method to reduce excessive water production in fractured reservoirs. However, previous research on its plugging effic...

Endogenous and exogenous signals are perceived and integrated by plants to precisely control defense responses. As a crucial environmental cue, light reportedly plays vital roles in plant defenses against necrotrophic pathogens. Phytochrome-interacting factor (PIF) is one of the important transcription factors which plays essential roles in photoreceptor-mediated light response. In this study, we revealed that PIFs negatively regulate plant defenses against Botrytis cinerea. Gene expression analyses showed that the expression level of a subset of defense-response genes was higher in pifq (pif1/3/4/5) mutants than in the wild-type control, but was lower in PIF-overexpressing plants. Chromatin immunoprecipitation assays proved that PIF4/5 binds directly to the ETHYLENE RESPONSE FACTOR1 (ERF1) promoter. Moreover, genetic analyses indicated that the overexpression of ERF1 dramatically rescues the susceptibility of PIF4-HA and PIF5-GFP transgenic plants, and that PIF controls the resistance to B. cinerea in a COI1- and EIN2-dependent manner. Our results provide compelling evidence that PIF, together with the jasmonate/ethylene pathway, is important for plant resistance to B. cinerea.

Role of polymer on foam transportation in porous media is still not entirely illustrated. In this study, we performed the foam injection process in cores and the parallel-layered micromodel, respectively. Combined with a series of static investigations, we found that adding polymer to foam could not only effectively generate a viscous force, but also create a protective enclosure around the bubble (i.e., viscoelastic film). This synergistic effect was supposed to increase the foam apparent viscosity, promote the foam strength in the low-quality regime, create the shear-thickening behavior, and restraint the defoaming effect of crude oil. The microflow experiments indicated that polymer-enhanced foam was capable of sharply increasing the sweep efficiency and EOR. Meanwhile, the presence of viscoelastic liquid films contributed to the microflow behaviors.

APG can be employed as a promising foaming agent due to its largely independent of temperature and salinity. Aiming at the APGs foam, we conducted the experiments about adsorption behaviors, surface viscoelasticity, bulk foam properties and core flooding under conditions of high-temperature and -salinity. Our results demonstrated that APG (n = 10) foam presents a good foam performance and foam properties are highly depended on the surface viscoelasticity and are not completely determined by the adsorbing capacity at the interface of gas–water. In the porous media, an appropriate foam quality of APG foam is contributed to increase the foam strength and gas trapping.

Smoke inhalation injury is the main cause of fatalities for fire victims. Understanding in the pathophysiology of the injury has not been fully explored in recent years. To further explore the pathophysiological mechanism, a dynamic and controllable animal model is necessary.To develop a rat model of smoke inhalation injury to simulate human victims in air-restricted vehicle cabin fires.Smoke concentration, including CO, O2, VOCs and smoke temperature under different combustion conditions, were detected. Levels of COHb, respiratory function, lung wet-to-dry weight ratio and protein concentration in BALF and blood were measured. Pathological evaluations of lung in tissues were conducted at 1, 6, 24 and 48 h post-exposure.Smoke concentration rose with the increase of combustion temperature and decrease of oxygen flow. Further, 215 kinds of VOCs in the smoke were detected, and the concentrations of benzene, methylbenzene, ethylbenzene, dimethylbenzene, phenylethylene and trimethylbenzene was 32.93, 402.06, 764.03, 113.73, 1006.61 and 89.28 mg/m(3), respectively. Significant hypoxemia and CO poisoning occurred in rats. The FCOHb after exposure for 14 min immediately rose to (44.2 ± 12.3) % and then gradually decrease to a normal level at 300 min post-exposure. At 24 h post-exposure, Penh increased significantly (p 0.05), and high pulmonary vascular permeability and significant lung edema (p 0.05) were observed in the smoke inhalation group.In summary, the novel rat model of smoke inhalation injury system used in the study is dynamic and controllable, and appropriate for use in smoke inhalation injury studies of air-restricted cabins in vehicles.

Leaf senescence can be triggered and promoted by various environmental stressors, developmental cues, and endogenous hormone signals. Several lines of evidence have suggested the involvement of WRKY transcription factors in regulating leaf senescence, but the underlying mechanisms and signaling pathways involved remain elusive. In this study, we identified Arabidopsis thaliana WRKY DNA-binding protein 45 (WRKY45) as a positive regulator of age-triggered leaf senescence. Loss of WRKY45 function resulted in increased leaf longevity in age-triggered senescence, whereas overexpression of WRKY45 significantly accelerated age-triggered leaf senescence. Consistently, expression of SENESCENCE-ASSOCIATED GENEs (SAGs) was significantly reduced in wrky45 mutants but markedly enhanced in transgenic plants overexpressing WRKY45. Chromatin immunoprecipitation assays revealed that WRKY45 directly binds the promoters of several SAGs such as SAG12, SAG13, SAG113, and SEN4. Both in vivo and in vitro biochemical analyses demonstrated that WRKY45 interacts with the DELLA protein RGA-LIKE1 (RGL1), a repressor of the gibberellin (GA) signaling pathway. We found that RGL1 repressed the transcription activation function of WRKY45, thereby attenuating the expression of its regulon. Consistent with this finding, overexpression of RGL1 resulted in significantly increased leaf longevity in age-triggered senescence. Taken together, our results provide compelling evidence that WRKY45 functions as a critical component of the GA-mediated signaling pathway to positively regulate age-triggered leaf senescence.

Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) simultaneously exist in polluted food and water in humid and warm areas, and each has been reported to be genotoxic to liver and associated with hepatocellular carcinoma (HCC). However, the genotoxic effects of the two biotoxins in combination and potential mechanism remain unknown. We treated the human hepatic cell line HL7702 with AFB1 and MC-LR together at different ratios, examined their genotoxic effects using micronuclei and comet assays, and evaluated the possible mechanism by measuring oxidative stress markers and DNA base excision repair (BER) genes. Our data show that co-exposure to AFB1 and MC-LR significantly increased DNA damage compared with AFB1 or MC-LR alone as measured by the levels of both micronuclei and tail DNA. Meanwhile, AFB1 and MC-LR co-exposure showed biphasic effects on ROS production, and a gradual trend towards increased Glutathione (GSH) levels and activity of Catalase (CAT) and Superoxide Dismutase (SOD). Furthermore, MC-LR, with or without AFB1, significantly down-regulated the expression of the base excision repair (BER) genes 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross complementing group 1 (XRCC1). AFB1 and MC-LR in combination upregulated the expression of the BER gene apurinic/apyrimidinic endonuclease 1 (APE1), whereas either agent alone had no effect. In conclusion, our studies show that MC-LR exacerbates AFB1-induced genotoxicity and we report for the first time that this occurs through effects on oxidative stress and the deregulation of DNA base excision repair genes.

1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78‰ versus 5.62 ± 2.41‰) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79‰ versus 1.13 ± 1.34‰) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.

WRKY transcription factors are key players in the plant immune response, but less is known about their involvement in antiviral defense than about their roles in defense against bacterial or fungi pathogens. Here, we report that Arabidopsis thaliana WRKY DNA-binding protein 8 (WRKY8) has a role in mediating the long-distance movement of crucifer-infecting tobacco mosaic virus (TMV-cg). The expression of WRKY8 was inhibited by TMV-cg infection, and mutation of WRKY8 accelerated the accumulation of TMV-cg in systemically infected leaves. Quantitative RT-PCR analysis showed that the expression of ABA insensitive 4 (ABI4) was reduced and the expression of 1-aminocyclopropane-1-carboxylic acid synthase 6 (ACS6) and ethylene response factor 104 (ERF104) was enhanced in the systemically infected leaves of wrky8. Immunoprecipitation assays demonstrated that WRKY8 could bind selectively to putative W-boxes of the ABI4, ACS6, and ERF104 promoters. Furthermore, TMV-cg infection enhanced WRKY8 binding to the ABI4 promoter but reduced the binding of WRKY8 to the ACS6 and ERF104 promoters, indicating that regulation of ABI4, ACS6, and ERF104 by WRKY8 is at least partially dependent on TMV-cg. Exogenous applications of abscisic acid (ABA) reduced the systemic accumulation of TMV-cg. Mutations in ABA deficient 1, ABA deficient 2, ABA deficient 3, or abi4 accelerated systemic TMV-cg accumulation. In contrast, exogenous application of aminocyclopropane-1-carboxylic acid enhanced the systemic accumulation of TMV-cg, but mutations in acs6, erf104, or an octuple acs mutant inhibited systemic TMV-cg accumulation. Our results demonstrate that WRKY8 is involved in the defense response against TMV-cg through the direct regulation of the expression of ABI4, ACS6, and ERF104 and may mediate the crosstalk between ABA and ethylene signaling during the TMV-cg–Arabidopsis interaction.

To evaluate the clinic manifestation, pathologic behavior, therapy and prognosis of rare aggressive fibromatosis in the head and neck.Two cases of aggressive fibromatosis were analyzed and relevant literatures were reviewed.Aggressive fibromatosis was characterized as infiltrative, locally aggressive and tended to recur after surgical resection. Pathology showed fibroblastic monoclonal proliferation. Fibromatosis was composed of well-differentiated fibroblasts and myofibroblasts, lacking cytological features of malignancy and scanty or absent mitotic activity. Complete surgical excision of aggressive fibromatosis was considered to be the only effective method of cure by most authorities. Chemotherapy and radiotherapy can be used together with surgery in recurrence or unsatisfactory surgical margin. In our study, one patient recurred after the first operation, and after another operation, the patient did not recur after 6 months follow up, and the other one did not recur after 6 months follow up.The diagnosis of aggressive fibromatosis depended on pathological examination. Radical removal was an important way to reduce recurrence rate. Radiation therapy and chemotherapy can be used as adjuvant therapy in patients with recurrent or unresectable or inoperable disease.