Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have ...suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown. In the present study, we first showed that TRIM21 could promote OS cell autophagy, as determined by the accumulation of LC3-II, and the degradation of cargo receptor p62. Further, we were able to identify that Annexin A2 (ANXA2), as a novel interacting partner of TRIM21, was critical for TIRM21-induced OS cell autophagy. Although TRIM21 had a negligible effect on the mRNA and protein expressions of ANXA2, we did find that TRIM21 facilitated the translocation of ANXA2 toward plasma membrane (PM) in OS cells through a manner relying on TRIM21-mediated cell autophagy. This functional link has been confirmed by observing a nice co-expression of TRIM21 and ANXA2 (at the PM) in the OS tissues. Mechanistically, we demonstrated that TRIM21, via facilitating the ANXA2 trafficking at the PM, enabled to release the transcription factor EB (TFEB, a master regulator of autophagy) from the ANXA2-TFEB complex, which in turn entered into the nucleus for the regulation of OS cell autophagy. In accord with previous findings that autophagy plays a critical role in the control of differentiation, we also demonstrated that autophagy inhibited OS cell differentiation, and that the TRIM21/ANXA2/TFEB axis is implicated in OS cell differentiation through the coordination with autophagy. Taken together, our results suggest that the TRIM21/ANXA2/TFEB axis is involved in OS cell autophagy and subsequent differentiation, indicating that targeting this signaling axis might lead to a new clue for OS treatment.
The brown planthopper (
Nilaparvata lugens
Stål; BPH) is the most destructive rice pests worldwide. Identification and application of major resistance genes and cultivation of resistant varieties are ...the most efficient methods to control this insect. In this study, the rice variety, ARC5984, was detected to be highly resistant to BPH due to the presence of a major resistance gene, which has primarily been mapped in a 6-cM region on the long arm of chromosome 4. Fine mapping of the resistance gene was performed using the recombinants derived from BC
1
F
2
individuals; the target gene was described to be a 46-kb region in the Nipponbare genome. Based on the information on the genomic sequences of the varieties Nipponbare, ZS97 and MH63, six, seven and 11 candidate genes were identified in the finally located region, respectively. The relative expression of the candidate genes
Os04g35190
and
Os04g35210
was significantly different between the resistant and susceptible plants after BPH infestation. The sequencing results indicated the coding domain sequence (CDS) of
Os04g35210
from ARC5984 to be identical to that of
Bph6
. But the CDS of
Os04g35190
was different between in ARC5984 and 9311. Moreover, the preliminary-near-isogenic lines (pre-NILs; the lines carrying resistance genes) with genetic background of the 9311 showed significant antixenosis to BPH, and thus, restricted its growth and development when compared with that in the susceptible line of 9311. Finally, a marker-assisted selection (MAS) technique was developed for the markers, RM5635 and BF9; its efficiency has been confirmed by applying it in screening of backcrossed individuals. The development in the fine mapping of the major gene will facilitate efforts of cloning this important resistance gene and to apply it in breeding of BPH-resistance rice varieties.
Rice planthoppers, including brown planthopper (BPH) and white-backed planthopper (WBPH), are the most destructive pests in Asian rice cultivation regions. Planthopper resistance genes that have been ...mapped and characterized advance our understanding of underlying resistance mechanisms and facilitate the breeding of resistant varieties, thereby contributing to an efficient pest management strategy. In this study, a novel resistance gene Bph38 derived from the wild rice species Oryza rufipogon Griff. was found to confer high resistance to BPH and WBPH. Conventional mapping was performed to identify regions associated with BPH and WBPH resistance, and two mapping efforts led to the same region on chromosome 4 flanked by markers RM16563 and RM16763. Bulked-segregant analysis and next-generation sequencing were performed using the same population to detect the resistance gene. Conventional mapping narrowed the region to a 12.3-Mb segment, and fine mapping using BC1F2 recombinants identified a 79-kb segment flanked by markers YM112 and YM190. Near-isogenic lines (NILs) carrying Bph38 in the 9311 (indica) and BR54 (japonica) genetic backgrounds were developed by crossing and backcrossing with marker-assisted selection. The agronomic traits and BPH and WBPH resistance of the NILs were similar to those of the recurrent parents. Mandatory feeding and host-choice tests revealed that Bph38 showed both antibiotic and antixenotic effects in both insects, with stronger effects in indica-background lines. Further fine mapping and characterization of the major gene may result in map-based cloning of the gene and allow its application in breeding insect-resistant rice varieties.
This study describes the ultrasonic time-domain reflectometry (UTDR) with a sound intensity calculation for monitoring membrane scaling and cleaning in a 4-inch spiral-wound reverse osmosis module. ...Three focused transducers with the frequency of 2.25
MHz were located equidistantly along the feed flow direction. The scaling experiments were carried out with 2.0
g/L calcium sulfate for 90
h fouling and the cleaning processes consisted of three phases: pure water flushing, immersion cleaning and acid-washing. According to this study, the ultrasonic response signals and the corresponding sound intensity gradually decreased to minimum with the fouling and deposition of the foulants on the membrane and then increased with the formation of fouling layer. The initial induction time in the change of sound intensity became shorter and the sound intensity became lower along the fluid direction during the fouling process. It was found that the CaSO
4 scaling first precipitated near the downstream owing to the increased concentration polarization. Furthermore, the permeate flux and the sound intensity all recovered step by step with the cleaning processes. The results obtained by independent methods such as SEM and weight measurements were in good agreement with the observations by ultrasonic technology. Overall, this study confirms that the UTDR technique with a sound intensity calculation and modeling is capable to evaluate the membrane scaling and cleaning in spiral-wound modules.
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► The UTDR technique with the sound intensity calculation has been developed to detect membrane scaling and cleaning in spiral-wound RO membrane modules. ► The initial induction time in the changes of the relative sound intensity became shorter and the sound intensity became lower along the fluid direction during the scaling experiment. ► The CaSO4 scaling first precipitated near the down stream. ► Both the permeate flux and the sound intensity recovered step by step with the cleaning processes.
The ultrasonic time-domain reflectometry (UTDR) technique with a new signal analysis protocol-sound intensity calculation and modeling was developed to detect the calcium-sulfate fouling in a ...commercial spiral-wound reverse osmosis (RO) membrane module. The fouling experiments were carried out with 2.0 g/L calcium sulfate solution. A 2.25 MHz focused transducer was used and mounted on the outside of the module housing. Results show that the ultrasound is capable to penetrate through the multiple layers of membrane. The systematic changes on the ultrasonic reflected signals with fouling time were observed by UTDR. The total sound intensity of the response signals obtained declined with the fouling time and reached a minimum at about 25 h of fouling, and then increased in the following time. The changes in the total sound intensity were correlated to the deposition and formation of the fouling. The entire acoustic spectra were divided into three sections according to the arrival time. The subsection sound intensity indicated that the fouling layers deposited on the membranes in regular order from inner to outer of the spiral-wound module. Gravimetric and scanning electron microscopy (SEM) analyses revealed the membranes near the pure water tube of the module suffered from much severely fouling. Overall, this study demonstrates that the UTDR with a suitable signal analysis protocol can provide valuable insight concerning fouling in a spiral-wound membrane module.
Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown ...that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.
Oil fouling during crossflow microfiltration of oily wastewater using a single hollow fiber membrane filtration module as outside-in conformation was analyzed experimentally by ultrasonic ...reflectometry and wavelet transform in real time. Three 10
MHz ultrasonic sensors mounted along the tubular test module were utilized to monitor the fouling profile of the hollow fiber membrane. Results showed that the instantaneously rapid flux decline at the onset of fouling was caused mainly by concentration polarization and the fast oil adsorption on the lower part of the hollow fiber near the inlet of the membrane module. Further, wavelet analysis of the ultrasonic spectra revealed that the amount of oil deposited on the lower part of the hollow fiber near the inlet of the membrane module was more than those on the other parts of the hollow fiber due to the inertial impaction of oil droplets and local shell-side hydrodynamic effects. Moreover, the oil diffusion behavior (the relaxation and disappearance of the fouling layer) was also visualized by ultrasonic reflectometry in real time after the microfiltration system was shut down. The flux decline data and SEM micrographs corroborated the ultrasonic measurements and wavelet analysis. Overall, this technique will provide a useful and quantitative approach to the on-line assessment of fouling remediation and cleaning strategies of hollow fiber membranes.
Objective. The aim of this study is to explore and analyze the high risk factors and preventive measures of percutaneous nephrolithotomy under the guidance of B-ultrasound in the treatment of ...postoperative renal calculi. Methods. The clinical data of 220 patients with renal calculi admitted to our hospital from 2018 to October 2021 were retrospectively analyzed. All patients were treated with percutaneous nephrolithotomy n = 36) and nonbleeding group (n = 184), comparing the personal data, disease-related data, surgical operation related data of the two groups of patients, single factor and logistic multifactor regression analysis to explore the influence of B-guided percutaneous. Nephrolithotomy is a high-risk factor for postoperative bleeding in patients with kidney stones, and preventive measures are based on high-risk factors. Results. There was no significant difference in the proportion of patients with different genders, whether they had renal surgery, whether they had hypertension, and those with postoperative hepatic insufficiency in the hemorrhagic group and the nonbleeding group (p>0.05). There was no significant difference in age and body mass index between the bleeding group and the nonbleeding group (p>0.05). The proportion of patients with diabetes in the bleeding group was higher than that in the nonbleeding group, and the difference between the groups was statistically significant (p<0.05). Compared with the nonbleeding group, the bleeding group had a higher proportion of patients with calculus diameter ≥2 cm. The proportion of patients with staghorn calculi in the bleeding group was higher than that in the nonbleeding group. The difference between the groups was statistically significant (p<0.05). There was no significant difference in the proportion of patients with hemorrhage, single or multiple renal stones, and ureteral stones in the hemorrhage group compared with the nonbleeding group (p>0.05). Compared with the nonbleeding group, the proportion of patients with bleeding in the first stage was higher, and the proportion of patients with operation time >90 min was higher. The difference between the groups was statistically significant (p<0.05). There was no significant difference in the proportion of patients in the bleeding group compared with the nonbleeding group (p>0.05). Using Logic multifactorial regression analysis, independent risk factors for bleeding after percutaneous nephrolithotomy under ultrasound-guided bovery include diabetes mellitus, stone diameter, staghorn kidney stones, surgical timing, and staging surgery (p<0.05). Conclusion. The independent high-risk factors affecting bleeding after percutaneous nephrolithotomy guided by B-ultrasound include diabetes, stone diameter, staghorn type kidney stones, operation time, and staged surgery. According to this, effective preventive measures can effectively reduce the operation and the occurrence of postbleeding.
Chondrosarcoma is the second-most common type of bone tumor and has inherent resistance to conventional chemotherapy. Present study aimed to explore the therapeutic effect and specific mechanism(s) ...of combination BET family protein and HDAC inhibition in chondrosarcoma.
Two chondrosarcoma cells were treated with BET family protein inhibitor (JQ1) and histone deacetylase inhibitors (HDACIs) (vorinostat/SAHA or panobinostat/PANO) separately or in combination; then, the cell viability was determined by Cell Counting Kit-8 (CCK-8) assay, and the combination index (CI) was calculated by the Chou method; cell proliferation was evaluated by 5-ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assay; cell apoptosis and reactive oxygen species (ROS) level were determined by flow cytometry; protein expressions of caspase-3, Bcl-XL, Bcl-2, γ-H2AX, and RAD51 were examined by Immunoblotting; DNA damage was determined by comet assay; RAD51 and γ-H2AX foci were observed by immunofluorescence.
Combined treatment with JQ1 and SAHA or PANO synergistically suppressed the growth and colony formation ability of the chondrosarcoma cells. Combined BET and HDAC inhibition also significantly elevated the ROS level, followed by the activation of cleaved-caspase-3, and the downregulation of Bcl-2 and Bcl-XL. Mechanistically, combination treatment with JQ1 and SAHA caused numerous DNA double-strand breaks (DSBs), as evidenced by the comet assay. The increase in γ-H2AX expression and foci formation also consistently indicated the accumulation of DNA damage upon cotreatment with JQ1 and SAHA. Furthermore, RAD51, a key protein of homologous recombination (HR) DNA repair, was found to be profoundly suppressed. In contrast, ectopic expression of RAD51 partially rescued SW 1353 cell apoptosis by inhibiting the expression of cleaved-caspase-3.
Taken together, our results disclose that BET and HDAC inhibition synergistically inhibit cell growth and induce cell apoptosis through a mechanism that involves the suppression of RAD51-related HR DNA repair in chondrosarcoma cells.
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