In diverse conditions, intrinsic chromatin condensates have liquid-like material properties.

Nuclear DNA in eukaryotes is wrapped around histone proteins to form nucleosomes on a chromatin fiber. Dynamic folding of the chromatin fiber into loops and variations in the degree of chromatin compaction regulate essential processes such as transcription, recombination, and mitotic chromosome segregation. Our understanding of the physical properties that allow chromatin to be dynamically remodeled even in highly compacted states is limited. Previously, we reported that chromatin has an intrinsic capacity to phase separate and form dynamic liquid-like condensates, which can be regulated by cellular factors [B. A. Gibson et al., Cell 179, 470-484.e421 (2019)]. Recent contradictory reports claim that a specific set of solution conditions is required for fluidity in condensates that would otherwise be solid [J. C. Hansen, K. Maeshima, M. J. Hendzel, Epigenetics Chromatin 14, 50 (2021); H. Strickfaden et al., Cell 183, 1772-1784.e1713 (2020)]. We sought to resolve these discrepancies, as our ability to translate with confidence these biophysical observations to cells requires their precise characterization. Moreover, whether chromatin assemblies are dynamic or static affects how processes such as transcription, loop extrusion, and remodeling will engage them inside cells. Here, we show in diverse conditions and without specific buffering components that chromatin fragments form phase separated fluids in vitro. We also explore how sample preparation and imaging affect the experimental observation of chromatin condensate dynamics. Last, we describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained chromatin movement observed in cells.

Dynamic network reorganization underlying neuroplasticity: the deficits-severity-related language network dynamics in patients with left hemispheric gliomas involving language network.

Brain network dynamics not only endow the brain with flexible coordination for various cognitive processes but also with a huge potential of neuroplasticity for development, skill learning, and after cerebral injury. Diffusive and progressive glioma infiltration triggers the neuroplasticity for functional compensation, which is an outstanding pathophysiological model for the investigation of network reorganization underlying neuroplasticity. In this study, we employed dynamic conditional correlation to construct framewise language networks and investigated dynamic reorganizations in 83 patients with left hemispheric gliomas involving language networks (40 patients without aphasia and 43 patients with aphasia). We found that, in healthy controls (HCs) and patients, the language network dynamics in resting state clustered into 4 temporal-reoccurring states. Language deficits-severity-dependent topological abnormalities of dFCs were observed. Compared with HCs, suboptimal language network dynamics were observed for those patients without aphasia, while more severe network disruptions were observed for those patients with aphasia. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the 4 states significantly predicted individual patients' language scores. These findings shed light on our understanding of metaplasticity in glioma. Glioma-induced language network reorganizations were investigated under a dynamic "meta-networking" (network of networks) framework. In healthy controls and patients with glioma, the framewise language network dynamics in resting-state robustly clustered into 4 temporal-reoccurring states. The spatial but not temporal language deficits-severity-dependent abnormalities of dFCs were observed in patients with left hemispheric gliomas involving language network. Language network dynamics significantly predicted individual patients' language scores.

Recycling and high-value utilization of polyethylene terephthalate wastes: A review.

Polyethelene terephthalate (PET) is a well-known thermoplastic, and recycling PET waste is important for the natural environment and human health. This study provides a comprehensive overview of the recycling and reuse of PET waste through energy recovery and physical, chemical, and biological recycling. This article summarizes the recycling methods and the high-value products derived from PET waste, specifically detailing the research progress on regenerated PET prepared by the mechanical recycling of fiber/yarn, fabric, and composite materials, and introduces the application of PET nanofibers recycled by physical dissolution and electrospinning in fields such as filtration, adsorption, electronics, and antibacterial materials. This article explains the energy recovery of PET through thermal decomposition and comprehensively discusses various chemical recycling methods, including the reaction mechanisms, catalysts, conversion efficiencies, and reaction products, with a brief introduction to PET biodegradation using hydrolytic enzymes provided. The analysis and comparison of various recycling methods indicated that the mechanical recycling method yielded PET products with a wide range of applications in composite materials. Electrospinning is a highly promising recycling strategy for fabricating recycled PET nanofibers. Compared to other methods, physical recycling has advantages such as low cost, low energy consumption, high value, simple processing, and environmental friendliness, making it the preferred choice for the recycling and high-value utilization of waste PET.

Enhancing Inverted Internal Limiting Membrane Flap Stability in Macular Hole Retinal Detachment by the "Viscoelastic Agent Pool" Technique.

PURPOSE: To evaluate the surgical, anatomical, and functional results of "viscoelastic agent pool" technique-assisted stability of inverted internal limiting membrane flap in macular hole retinal detachment. METHODS: The innovative surgical technique was performed on 10 patients with macular hole retinal detachment. The primary outcomes included best-corrected visual acuity after surgery, rate of closure of macular hole, retinal reattachment, and occurrence of complications. RESULTS: The mean age of the individuals was 67.70 ± 8.75 (range, 55-84) years; mean axial length, 29.34 ± 1.53 (range, 27.10-30.93) mm; mean corrected MH diameter, 685.30± 345.65 (range, 172-1,325) µ m; and average follow-up period, 6.01 ± 1.71 (range, 3.10-8.4) months. In 6 eyes (60%), the postoperative best-corrected visual acuity showed improvement. All patients had macular hole closure, and the retinal reattachment rate was 100%. No postoperative complications were noted. CONCLUSION: The "viscoelastic agent pool" technique, an innovative surgical approach designed to enhance the stability of the internal limiting membrane flap, serves as an effective adjunctive procedure for the inverted internal limiting membrane flap technique. It presents a viable option for patients with macular hole retinal detachment.

Risk Factors of Chronic Pulmonary Aspergillosis in Patients with Etiology Positive Pulmonary Tuberculosis.

Objective: Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) have many similarities in clinical symptoms. In patients with etiology-positive pulmonary tuberculosis (EPTB), Aspergillus infection is easily overlooked, and missed diagnosis occurs. We attempted to analyze the clinical characteristics and risk factors of EPTB combined with CPA (EPTB-CPA), and to suggest to clinicians the possibility of CPA in EPTB patients. Methods: 58 patients with EPTB-CPA diagnosed and treated in Wuhan Pulmonary Hospital from April 2021 to March 2022 were retrospectively collected as the case group. According to the age group of the case group, 174 patients with EPTB were randomly selected as the control group at a ratio of 1:3. Multivariate logistic regression analysis was utilized to analyze the risk factors. Results: Multivariate Logistic regression analysis was performed on the pulmonary cavity, chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, lung damage, anemia, and hypoproteinemia. Among them, pulmonary cavity (P = .001), COPD (P = .006), and bronchiectasis (P = .020) were statistically significant. Conclusion: Our findings suggest that when EPTB patients present with pulmonary cavities and comorbidities such as COPD or bronchiectasis, clinicians should consider the possibility of CPA. Identifying these risk factors can help improve the accuracy of diagnosis and facilitate early detection and management of EPTB-CPA.

Novel phosphate functionalized sodium alginate hydrogel for efficient adsorption and separation of Nd and Dy from Co.

The recovery of rare earth elements (REEs) including neodymium (Nd) and dysprosium (Dy) from NdFeB permanent magnets has become one of the main ways to solve the increased demand for rare earth. Herein, n-dodecyl phosphate (DPPA) was used for the first time as the adsorption functional group donor, sodium alginate as the substrate, and calcium chloride solution as the reactive solvent, a hybrid hydrogel adsorbent DPPA/CaALG was synthesized by sol-gel method for application in the adsorption and separation of Nd and Dy from the Co-Nd-Dy ternary system. SEM-EDS, and N2 adsorption-desorption analysis showed the successful preparation of DDPA/CaALG with mesoporous structure. Batch experiments showed the superiority of the hybrid hydrogel for the good selective adsorption of Nd and Dy, such as large adsorption capacity (Nd: 162.5 mg/g, Dy: 183.5 mg/g), and no adsorption for Co. FT-IR, XPS showed that PO and P-O groups are involved in the adsorption process of Nd and Dy as electron acceptors, where the ion exchange of P-OH is dominant. Furthermore, the chemical properties of ligands and complexes were analyzed by Density Functional Theory (DFT) calculations and revealed their adsorption behaviors as well as the competition between different metal ions.

The domain-separation language network dynamics in resting state support its flexible functional segregation and integration during language and speech processing.

Modern linguistic theories and network science propose that language and speech processing are organized into hierarchical, segregated large-scale subnetworks, with a core of dorsal (phonological) stream and ventral (semantic) stream. The two streams are asymmetrically recruited in receptive and expressive language or speech tasks, which showed flexible functional segregation and integration. We hypothesized that the functional segregation of the two streams was supported by the underlying network segregation. A dynamic conditional correlation approach was employed to construct framewise time-varying language networks and k-means clustering was employed to investigate the temporal-reoccurring patterns. We found that the framewise language network dynamics in resting state were robustly clustered into four states, which dynamically reconfigured following a domain-separation manner. Spatially, the hub distributions of the first three states highly resembled the neurobiology of speech perception and lexical-phonological processing, speech production, and semantic processing, respectively. The fourth state was characterized by the weakest functional connectivity and was regarded as a baseline state. Temporally, the first three states appeared exclusively in limited time bins (∼15%), and most of the time (> 55%), state 4 was dominant. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the four states significantly predicted individual linguistic performance. These findings suggest a domain-separation manner of language network dynamics in resting state, which forms a dynamic "meta-network" framework to support flexible functional segregation and integration during language and speech processing.

PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K.

Phosphoinositide-3 kinase (PI3K) signaling regulates many cellular processes, including cell survival, differentiation, proliferation, cytoskeleton reorganization, and apoptosis. The actin cytoskeleton regulated by PI3K signaling plays an important role in plasma membrane rearrangement. Currently, it is known that respiratory syncytial virus (RSV) infection requires PI3K signaling. However, the regulatory pattern or corresponding molecular mechanism of PI3K signaling on cell-to-cell fusion during syncytium formation remains unclear. This study synthesized a novel PI3K inhibitor PIK-24 designed with PI3K as a target and used it as a molecular probe to investigate the involvement of PI3K signaling in syncytium formation during RSV infection. The results of the antiviral mechanism revealed that syncytium formation required PI3K signaling to activate RHO family GTPases Cdc42, to upregulate the inactive form of cofilin, and to increase the amount of F-actin in cells, thereby causing actin cytoskeleton reorganization and membrane fusion between adjacent cells. PIK-24 treatment significantly abolished the generation of these events by blocking the activation of PI3K signaling. Moreover, PIK-24 had an obvious binding activity with the p85α regulatory subunit of PI3K. The anti-RSV effect similar to PIK-24 was obtained after knockdown of p85α in vitro or knockout of p85α in vivo, suggesting that PIK-24 inhibited RSV infection by targeting PI3K p85α. Most importantly, PIK-24 exerted a potent anti-RSV activity, and its antiviral effect was stronger than that of the classic PI3K inhibitor LY294002, PI-103, and broad-spectrum antiviral drug ribavirin. Thus, PIK-24 has the potential to be developed into a novel anti-RSV agent targeting cellular PI3K signaling. IMPORTANCE PI3K protein has many functions and regulates various cellular processes. As an important regulatory subunit of PI3K, p85α can regulate the activity of PI3K signaling. Therefore, it serves as the key target for virus infection. Indeed, p85α-regulated PI3K signaling facilitates various intracellular plasma membrane rearrangement events by modulating the actin cytoskeleton, which may be critical for RSV-induced syncytium formation. In this study, we show that a novel PI3K inhibitor inhibits RSV-induced PI3K signaling activation and actin cytoskeleton reorganization by targeting the p85α protein, thereby inhibiting syncytium formation and exerting a potent antiviral effect. Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens, causing enormous morbidity, mortality, and economic burden. Currently, no effective antiviral drugs or vaccines exist for RSV infection. This study contributes to understanding the molecular mechanism by which PI3K signaling regulates syncytium formation and provides a leading compound for anti-RSV infection drug development.

PATHOLOGIC STUDY OF UNTREATED INTRARETINAL GLIOSIS SURGICALLY EXCISED VIA PARS PLANA VITRECTOMY.

PURPOSE: To evaluate the pathologic process of intraretinal glioses by investigating mass tissues resected from untreated eyes with intraretinal glioses. METHODS: Five patients with intraretinal gliosis without previous conservative treatment were included. All patients underwent pars plana vitrectomy. The mass tissues were excised and processed for the pathologic study. RESULTS: During surgery, it was observed that the intraretinal gliosis mainly affected the neuroretina and the retinal pigment epithelium was not affected. Pathologic examination revealed that all intraretinal glioses consisted of different proportions of hyaline vessels and hyperplastic spindle-shaped glial cells. In one case, the intraretinal gliosis was mainly composed of hyaline vascular components. In another case, the intraretinal gliosis showed a predominance of glial cells. The intraretinal glioses in the other three cases had vascular and glial components. The proliferated vessels showed different amounts of collagen deposits against different backgrounds. Vascularized epiretinal membrane was found in some intraretinal glioses. CONCLUSION: Intraretinal glioses affected the inner retinal layer. Hyaline vessels were the most characteristic pathologic changes; the proportion of proliferative glial cells varied in different intraretinal glioses. The natural course of intraretinal gliosis may involve the proliferation of abnormal vessels in the early stage, which then gradually become scarred and are replaced by glial cells.

Variational Bayesian Algorithms for Maneuvering Target Tracking with Nonlinear Measurements in Sensor Networks.

The variational Bayesian method solves nonlinear estimation problems by iteratively computing the integral of the marginal density. Many researchers have demonstrated the fact its performance depends on the linear approximation in the computation of the variational density in the iteration and the degree of nonlinearity of the underlying scenario. In this paper, two methods for computing the variational density, namely, the natural gradient method and the simultaneous perturbation stochastic method, are used to implement a variational Bayesian Kalman filter for maneuvering target tracking using Doppler measurements. The latter are collected from a set of sensors subject to single-hop network constraints. We propose a distributed fusion variational Bayesian Kalman filter for a networked maneuvering target tracking scenario and both of the evidence lower bound and the posterior Cramér-Rao lower bound of the proposed methods are presented. The simulation results are compared with centralized fusion in terms of posterior Cramér-Rao lower bounds, root-mean-squared errors and the 3σ bound.

Transmission of multidrug-resistant tuberculosis within family households by DTM-PCR and MIRU-VNTR genotyping.

BACKGROUND: Drug-resistant tuberculosis (TB) continues to be a public health threat. There are few studies on transmission and genotyping of MDR-TB family households in China. This study aimed to investigate transmission of multidrug-resistant tuberculosis (MDR-TB) within family households by deletion-targeted multiplex polymerase chain reaction (DTM-PCR), mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTR) genotyping. METHODS: Among 993 MDR-TB patients registered from Wuhan Institute for Tuberculosis Control, drug resistance and the time interval between the index patients and secondary patients were analyzed in 49 MDR-TB patients from 23 families, in which 22 MDR-TB strains from 11 families who had matched strains were genotyped by DTM-PCR and standard 24-loci MIRU-VNTR genotyping method. RESULTS: The time interval between the index patients and the secondary patients ranged from half a month to 110 months. Thirteen secondary patients developed active MDR-TB within two years and accounted for 50% (13/26) of all secondary patients. Among eleven pairs of MDR-TB families, six pairs had identical genotypes, the cluster rate was 54.5% (12/22); three pairs had a single MIRU-VNTR locus variation. If a single MIRU-VNTR locus variation was tolerated in the cluster definition, the cluster rate raised to 81.8% (18/22). CONCLUSIONS: The family households of MDR-TB patients are at risk for infection of MDR-TB. To reduce transmission, MDR-TB patients should be diagnosed earlier and promptly treated in an effective manner, meanwhile, the close family contacts should be screened for TB infection.

Early implementation of intended exercise improves quality of life in Parkinson's disease patients.

OBJECTIVE: Recent data have shown that regular exercise may ameliorate motor symptoms in Parkinson's disease (PD). This study aims to investigate how intended exercise impacts motor and non-movement symptoms of PD. METHODS: Eighty-eight patients were randomly assigned to an early exercise group (E-EG), late exercise group (L-EG), or a control group (CG) using a randomized delayed-start design. The E-EG carried out a rigorous, formal exercise program for 1 h, twice per week, for 18 months (May 2018-November 2019). The L-EG took part in the exercise program in the final 6-12 months of the study. We assessed outcomes using the Unified Parkinson's Disease Rating Scale (UPDRS), PDQ-39 Questionnaire, Line A test, Line B test, Nine-hole column test, 30 s squat and stand-up test (30 s SST), 10-m walk test (10mW), Balance Evaluation Systems Mini Test (MiniBESTest), FAB, and Time Up and Go Test (TUG). RESULTS: The patients with PD in the E-EG had lower performance in the UPDRS and Line B test compared to those in the L-EG at post-exercise (p < 0.05). Moreover, the patients with PD in the E-EG had much lower performance in the PDQ-39 and 9-Hole Peg test compared to those in the L-EG at post-exercise (p < 0.01). CONCLUSION: Implementation of an exercise regimen improved the movement abilities and quality of life in PD patients, especially in the E-EG. This data supports the idea that intended exercise should be implemented as part of the treatment strategy for PD patients as early as possible.

Spectral-domain optical coherence tomography characteristics of cystic retinal tuft.

OBJECTIVE: To investigate the characteristics of cystic retinal tufts (CRTs) with 55° widefield spectral-domain optical coherence tomography. METHODS: This was a retrospective study. All subjects underwent a complete ocular examination, ultra-widefield (UWF) pseudocolor fundus photography and Spectral domain optical coherence tomography (SD-OCT) with a 55° widefield lens. The SD-OCT characteristics were analyzed in subjects with CRT. RESULTS: Twenty-six eyes of 25 subjects were scanned and 29 CRTs were analyzed for SD-OCT characteristics. On SD-OCT images, the CRTs exhibited hyperreflective irregular elevated lesions with internal hyporeflective cystoid cavities. Normal layers of the neuroepithelium could not be distinguished. The mean diameter of CRTs was 1022 microns (range, 117-3711 microns; standard deviation, 815 microns). There was vitreoretinal traction at the apex of CRTs. Among them, retinal tears in 24.14% (7/29), suspected retinal tears in 27.59% (8/29), and shallow neuroepithelium detachment in 31.03% (9/29). CONCLUSIONS: The widefield SD-OCT imaging can provide detailed cross-sectional anatomic information of CRT and may guide clinical treatment.

Preliminary hysteroscopic tubal hydrotubation improves fertility outcomes after laparoscopic salpingotomy for tubal ampullary pregnancy.

BACKGROUND: Salpingotomy may change the anatomical structure and patency of the fallopian tube, which may affect the fallopian function. This study is to investigate the clinical efficacy of preliminary hysteroscopic tubal hydrotubation (HTH) after laparoscopic salpingotomy for tubal ampullary pregnancy. METHODS: A retrospective study was carried out, 140 women underwent laparoscopic salpingotomy for ampullary pregnancy from March 2013 to March 2017. Some patients received HTH in the 1st month and hysterosalpingography (HSG) in the 3rd month after salpingotomy (HTH group; n = 95), and some patients only received HSG in the 3rd month after salpingotomy (control group; n = 45). Clinical data, tubal patency and fertility outcome were evaluated after follow-up of 15 months. RESULTS: The tubal patency rate of the operated side was significantly higher in the HTH group than that in the control group (89.47% vs 68.89%, P < 0.05). The intrauterine pregnancy (IUP) rate was significantly higher in the HTH group (76.47% vs 51.11%, P < 0.05), and the recurrent ectopic pregnancy rate in the operated side was significantly lower in the HTH group than in the control group (9.41% vs 22.22%, P < 0.05). Logistic regression analysis showed that the positive factor for IUP was HTH (OR = 3.109, 95% CI 1.439-6.714, P = 0.004), while the negative factors were history of pelvic inflammatory disease (PID) (OR = 0.167, 95% CI 0.074-0.377, P < 0.001) and history of tubal infertility (OR = 0.286, 95% CI 0.113-0.723, P < 0.05). CONCLUSION: Preliminary HTH after laparoscopic salpingotomy for ampullary pregnancy could improve reproductive function and lead to a better fertility outcome. Patients without history of PID or tubal infertility may be the most suitable ones for HTH after salpingotomy.

Highly efficient removal of strontium from contaminated wastewater by a porous zirconium phosphate material.

Effective and efficient disposal of radioactive pollution has been crucial for responding to unexpected nuclear accidents and guaranteeing the sustainable development of nuclear energy. In this study, a kind of porous zirconium phosphate was synthesized with a sol-gel process followed by a post-synthesis modification to remove the radioactive Sr2+ from wastewater. The prepared materials were characterized by different technologies including FT-IR, SEM-EDS, XRD and XPS, and then the adsorption performance was evaluated in batch and column modes. Experimental results suggested that the porous zirconium phosphate adsorbent was successfully prepared with Na+ dispersed in the channels for exchange. It inherited the excellent properties of zirconium dioxide aerogel and exhibited mesoporous structure and large specific surface area. Compared with traditional zirconium phosphate, the adsorption kinetics and the adsorption capacity were improved simultaneously. Especially, it showed excellent selectivity towards Sr2+ among different cations, and even could remove the low-level Sr2+ from natural seawater efficiently, which powerfully demonstrated that the prepared material could be applied in the treatment of practical wastewater. Spectra studies uncovered that the adsorption activities were dominated by the ion exchange mechanism between external Sr2+ and interlaminar Na+ or H+. In conclusion, this paper not only reports a novel synthesis strategy for the acquisition of porous zirconium phosphate, but also presents a promising adsorbent for the Sr2+ removal.

Efficient four-way vertical coupler array for chip-scale space-division-multiplexing applications.

We propose and demonstrate a three-dimensional nano-printed four-channel vertical coupler array on the silicon-on-insulator platform for efficient chip-to-multicore fiber coupling. The proposed structure provides less than 1 dB loss in a single lane and around 2-4 dB loss in multicore fiber coupling, over 100 nm 1 dB bandwidth, and large 1 dB misalignment tolerances of more than 5 µm in the xy plane and 20 µm in the z direction. The device shows great promise for photonic integrated devices for space-division-multiplexing technology based on multicore fiber.

Reconfigurable silicon bandpass filters based on cascaded Sagnac loop mirrors.

We demonstrate a high-performance reconfigurable bandpass filter implemented by cascaded Sagnac loop mirror (SLM)-based coupled resonator optical waveguides (CROWs) on the silicon-on-insulator platform. By dynamic thermal tuning of the reflectivity in each SLM, the proposed filter can achieve simultaneous 3 dB bandwidth tuning from 8.50 to 20.25 GHz and a central wavelength tuning range of 216.25 GHz. A box-like filtering response with an ultra-high extinction ratio up to 70 dB and an ultra-sharp roll-off of 0.61 are observed in a 6th-order SLM-coupled resonator optical waveguide (SLM-CROW). The proposed reconfigurable SLM-CROW filter can satisfy the demand for next-generation flexible-grid WDM networks.

circ-PTTG1IP/miR-671-5p/TLR4 axis regulates proliferation, migration, invasion and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis.

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.

A self-designed liver circle for on-demand Pringle's manoeuver in laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection (LLR) allows minimal incisions and relatively quicker post-operative recovery, while intraoperative massive haemorrhage led to conversion to laparotomy. This study aimed to introduce a new, safe and convenient device to serve as Pringle's manoeuver according to the demand in LLR. METHODS: A liver circle consisting of a hole and a round stem with an obtuse small head was made by medical silica gel. It was applied in LLR to perform on-demand Pringle's manoeuver and developed its function in inferior vena cava (IVC) occlusion. The time of performing Pringle's manoeuver by liver circle, extracorporeal tourniquet and endo intestinal clip under laparoscopic simulator and LLR was compared. RESULTS: The liver circle was successfully applied to perform Pringle's manoeuver, IVC exposure and occlusion. It took less time in the occluding step of Pringle's manoeuver than the extracorporeal tourniquet (4.15 ± 0.35 s vs. 9.90 ± 1.15 s, P < 0.05) and the endo intestinal clip (4.15 ± 0.35 s vs. 47.91 ± 3.98 s, P < 0.05) under LLR. The total manipulating time for Pringle's manoeuver with liver circle remained the shortest, and the advantages were more obvious with increased frequencies of intermittent Pringle's manoeuver. CONCLUSION: The new-designed liver circle is more convenient compared to other techniques in performing Pringle's manoeuver, especially the intermittent Pringle's manoeuver in LLR. It can be used to perform on-demand hepatic blood inflow occlusion in every LLR by pre-circling the hepatoduodenal ligament to control bleeding during surgery. It can also be applied to expose the surgical field of vision and perform IVC occlusion to reduce intraoperative blood loss.

Inhibitory Effect of PIK-24 on Respiratory Syncytial Virus Entry by Blocking Phosphatidylinositol-3 Kinase Signaling.

Phosphoinositide-3 kinase signaling modulates many cellular processes, including cell survival, proliferation, differentiation, and apoptosis. Currently, it is known that the establishment of respiratory syncytial virus infection requires phosphoinositide-3 kinase signaling. However, the regulatory pattern of phosphoinositide-3 kinase signaling or its corresponding molecular mechanism during respiratory syncytial virus entry remains unclear. Here, the involvement of phosphoinositide-3 kinase signaling in respiratory syncytial virus entry was studied. PIK-24, a novel compound designed with phosphoinositide-3 kinase as a target, had potent anti-respiratory syncytial virus activity both in vitro and in vivo PIK-24 significantly reduced viral entry into the host cell through blocking the late stage of the fusion process. In a mouse model, PIK-24 effectively reduced the viral load and alleviated inflammation in lung tissue. Subsequent studies on the antiviral mechanism of PIK-24 revealed that viral entry was accompanied by phosphoinositide-3 kinase signaling activation, downstream RhoA and cofilin upregulation, and actin cytoskeleton rearrangement. PIK-24 treatment significantly reversed all these effects. The disruption of actin cytoskeleton dynamics or the modulation of phosphoinositide-3 kinase activity by knockdown also affected viral entry efficacy. Altogether, it is reasonable to conclude that the antiviral activity of PIK-24 depends on the phosphoinositide-3 kinase signaling and that the use of phosphoinositide-3 kinase signaling to regulate actin cytoskeleton rearrangement plays a key role in respiratory syncytial virus entry.