The liquid-to-solid transition of FUS is promoted by the condensate surface.

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions in biological systems. Crucially, however, a further liquid-to-solid transition of the condensates can lead to irreversible pathological aggregation and cellular dysfunction associated with the onset and development of neurodegenerative diseases. Despite the importance of this liquid-to-solid transition of proteins, the mechanism by which it is initiated in normally functional condensates is unknown. Here we show, by measuring the changes in structure, dynamics, and mechanics in time and space, that single-component FUS condensates do not uniformly convert to a solid gel, but rather that liquid and gel phases coexist simultaneously within the same condensate, resulting in highly inhomogeneous structures. Furthermore, our results show that this transition originates at the interface between the condensate and the dilute continuous phase, and once initiated, the gelation process propagates toward the center of the condensate. To probe such spatially inhomogeneous rheology during condensate aging, we use a combination of established micropipette aspiration experiments together with two optical techniques, spatial dynamic mapping and reflective confocal dynamic speckle microscopy. These results reveal the importance of the spatiotemporal dimension of the liquid-to-solid transition and highlight the interface of biomolecular condensates as a critical element in driving pathological protein aggregation.

Perioperative, functional, and oncologic outcomes of minimally-invasive surgery for highly complex renal tumors (RENAL or PADUA score ≥ 10): an evidence-based analysis.

The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] - 2.08 days, 95% confidence interval [CI] - 2.48, - 1.68; p < 0.00001), blood loss (WMD - 39.86 mL, 95% CI - 75.32, - 4.39; p = 0.03), transfusion rates (odds ratio [OR] 0.30, 95% CI 0.13, 0.71; p = 0.006), and overall complications (OR 0.46, 95% CI 0.31, 0.70; p = 0.0003). However, there were no significant differences between MIPN and OPN in terms of operative time, warm ischemia time, conversion to radical nephrectomy rates, renal functional and oncologic outcomes. This study reveals that MIPN presents several benefits in comparison to OPN, including decreased length of hospital stay, blood loss, transfusion rates, and complications, while still offering renal functional and oncological outcomes that are comparable to those of OPN in patients with highly complex renal tumors.

New Insights into Spin Coating of Polymer Thin Films in Both Wetting and Nonwetting Regimes.

Spin coating is a common method for fabricating polymer thin films on flat substrates. The well-established Meyerhofer relationship between film thickness (h) and spin rate (ω), h ∝ ω-1/2, enables the preparation of thin films with desired thickness by adjusting the spin rate and other experimental parameters. The 1/2 exponent has been verified by previous studies involving organic thin films prepared on silicon wafers. In this study, 88% and >99% hydrolyzed poly(vinyl alcohol) (PVOH) polymers were adsorbed and spin-coated from an aqueous solution onto four different substrates. The substrates were prepared by covalently attaching poly(dimethylsiloxane) (PDMS) of different molecular weights onto silicon wafers (SiO2). Atomic force microscopy images indicate that the PVOH films transitioned from stable on SiO2, to metastable, and then to unstable as PDMS molecular weight was increased. Notably, none of the polymer-substrate systems studied here exhibited the thickness-spin rate profile predicted by the Meyerhofer model. Based on the experimental results, a more general adsorption-deposition model is proposed that decouples the total spin-coated thickness into two components─the adsorbed thickness (h1) and the spin-deposited thickness (h2). The former accounts for polymer-substrate interactions, and the latter depends on polymer concentration and spin rate. In unstable systems, the exponents were found to be ∼0 because slip takes place at the solution-substrate interface during spin and the spin-deposited thickness is 0. In metastable and stable systems, a universal relationship between spin-deposited thickness and spin rate emerged, independent of the substrate type and polymer concentration for each polymer examined. Our findings indicate the importance of film stability and polymer-substrate interactions in the application of spin coating.

Effect of Cryotherapy plus Flurbiprofen Axetil for Pain Management in Children Undergoing Tonsillectomy.

Objective: To investigate the effect of cryotherapy using ice pops for physical analgesia and preventive analgesia using flurbiprofen axetil for pain management in children undergoing tonsillectomy. Methods: A total of 120 children scheduled for tonsillectomy were recruited after assessment for eligibility and assigned to a control group (group C), flurbiprofen axetil group (group F), cryotherapy group (group I), and cryotherapy plus flurbiprofen axetil group (Group FI) via the random number table method. Groups F and FI were given 1 mg/kg of flurbiprofen axetil through intravenous injection 30 min before surgery, while group C received an equal amount of saline at the same time point. Groups I and FI received sweet ice pops for pain relief after recovery from anesthesia. The modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) scores and pediatric anesthesia emergence delirium (PAED) scores at 5 minutes (T1), 30 minutes (T2), 60 minutes (T3), 4 hours (T4), and 24 hours (T5) postoperatively, and the incidence of postoperative complications in the children were recorded by investigators who were masked to the grouping results. Results: From T1 to T4, significantly lower mCHEOPS scores and PAED scores were observed in group F, group I, and group FI versus those in group C (P < 0.05). At T2, group FI showed significantly lower mCHEOPS scores and PAED scores versus groups F and I (P < 0.05). There were no significant differences in the mCHEOPS scores and PAED scores between the four groups at 24 h postoperatively (P > 0.05). The differences in the documented postoperative complications between the four groups did not come up to the statistical standard (P > 0.05). Conclusion: Cryotherapy plus flurbiprofen axetil for pain management significantly mitigates post-tonsillectomy pain and delirium in children and facilitates recovery, with no significant adverse events.

Synthesis of γ-Aminobutyric Acid-Modified Chitooligosaccharide Derivative and Enhancing Salt Resistance of Wheat Seedlings.

Salinity is one of the major abiotic stresses limiting crop growth and productivity worldwide. Salt stress during germination degenerates crop establishment and declines yield in wheat, therefore alleviating the damage of salt stress to wheat seedlings is crucial. Chitooligosaccharide (COS) was grafted with γ-aminobutyric acid based on the idea of bioactive molecular splicing, and the differences in salt resistance before and after grafting were compared. The expected derivative was successfully synthesized and exhibited better salt resistance-inducing activity than the raw materials. By activating antioxidant enzymes such as superoxide dismutases (SOD), catalase (CAT) and phenylalanine ammonia-lyase (PAL) and subsequently eliminating reactive oxygen species (ROS) in a timely manner, the rate of O-2 production and H2O2 content of wheat seedlings were reduced, and the dynamic balance of free radical metabolism in the plant body was maintained. A significantly reduced MDA content, reduced relative permeability of the cell membrane, and decreased degree of damage to the cell membrane were observed. A significant increase in the content of soluble sugar, maintenance of osmotic regulation and the stability of the cell membrane structure, effective reduction in the salt stress-induced damage to wheat, and the induction of wheat seedling growth were also observed, thereby improving the salt tolerance of wheat seedlings.

Advances in Artificial Layers for Stable Lithium Metal Anodes.

Lithium (Li) metal is considered as the most promising anode material for rechargeable high-energy batteries. Nevertheless, the practical implement of Li anodes is significantly hindered by the growth of Li dendrites, which can cause severe safety issues. To inhibit the formation of Li dendrites, coating an artificial layer on the Li metal anode has been shown to be a facile and effective approach. This review mainly focuses on recent advances in artificial layers for stable Li metal anodes. It summarizes the progress in this area and discusses the different types of artificial layers according to their mechanisms for Li dendrite inhibition, including regulation of uniform deposition of Li metal and suppression of Li dendrite growth. By doing this, it is hoped that this contribution will provide instructional guidance for the future design of new artificial layers.

Functional brain network topology in parents who lost their only child in China: Post-traumatic stress disorder and sex effects.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with disruption of the brain network topology; however, little is known about the topological changes and sex effects in PTSD patients following a unique trauma, the loss of an only child, in China. METHODS: Fifty-one lost-only-child parents with PTSD, 93 lost-only-child non-PTSD parents (NPTSD), and 50 healthy subjects underwent resting-state functional MRI. The whole-brain functional network was constructed by thresholding partial correlation matrices of 90 brain regions. Group differences in the topological properties, the diagnosis-by-sex interaction, and the relationships between topological metrics and clinical variables were investigated. RESULTS: Compared with healthy subjects, PTSD and NPTSD groups exhibited significantly shorter path lengths and higher nodal centralities in many brain regions across sexes; however, no significant difference was found between the PTSD and NPTSD groups. Additionally, the global topological metrics did not show any sex difference, whereas the nodal centralities in the left insula, right inferior frontal gyrus, and right posterior cingulate cortex differed significantly only in women, and the nodal centralities in the bilateral anterior cingulate cortices and left hippocampus were significantly different only in men. Furthermore, the nodal centralities of the right parahippocampus demonstrated significant diagnosis-by-sex interaction. LIMITATION: Cross-sectional design of this study could not demonstrate the causality. CONCLUSIONS: The parents who lost their only child exhibited a shift toward randomization and significant nodal topological alterations independent of PTSD effects. Additionally, sex differences were observed primarily in the topological properties at the nodal level, which may indicate a neurobiological contribution to the greater incidence of PTSD in females.

Adsorptive Spin Coating To Study Thin-Film Stability in Both Wetting and Nonwetting Regimes.

A new thin-film fabrication method, adsorptive spin coating, was evaluated in the preparation of poly(vinyl alcohol) (PVOH) thin films on silicon-wafer-supported poly(dimethylsiloxane) (PDMS) substrates. This method takes advantage of the rapid spontaneous adsorption of PVOH at the substrate-solution interface during the brief contact period and the directionality of drying during spinning. Similar to the results obtained using dip coating, the PVOH thin films wet the 2 kDa PDMS substrate and exhibit dewetted fractal morphologies on thicker PDMS substrates. This method generated PVOH films with thicknesses that were comparable to those prepared by dip coating except that thicker PVOH films were obtained at lower spin rates, following the Meyerhofer relationship in the wetting regime. Stepwise dewetting dynamics of confined PVOH drops were captured using high-speed photography. Drying and polymer aggregation initiate at the periphery of the drop and propagate toward the center of the drop. Each dewetted thin film adopts the footprint of the original drop and shows globally ordered patterns, which depend on both initial drop size and spin rate. The PVOH thin films have excellent stability toward water rinse if they are continuous and are given sufficient time to dry. This new adsorptive spin-coating method is not only straightforward but also unique in its ability to generate globally ordered morphologies that are the outcome of fast spontaneous adsorption, spin symmetry, and temporally and spatially adjustable drying rates. It is a valuable tool for fabricating a wide range of thin-film systems where surface adsorption/reaction is rapid, in both wetting and nonwetting regimes.

Inhibitory effect of an aqueous extract of Radix Paeoniae Alba on calcium oxalate nephrolithiasis in a rat model.

OBJECTIVE: To examine the effect of an aqueous extract of Radix Paeoniae Alba (RPA) on the formation of calcium oxalate (CaOx) stones and the potential mechanism underlying the effect. MATERIALS AND METHODS: An in vitro assay was used to determine whether the RPA extract prevents the formation of CaOx or promotes CaOx dissolution. We also investigated the efficacy of the extract in vivo as a preventive and therapeutic agent for experimentally induced CaOx nephrolithiasis in rats. Various biochemical, molecular, and histological parameters were assessed in kidney tissue and urine at the end of the in vivo experiment. RESULTS: Significant dissolution of formed crystals (8.99 ± 1.43) and inhibition of crystal formation (2.55 ± 0.21) were observed in vitro after treatment with 64 mg/mL of the RPA extract compared with a control treatment (55.10 ± 4.98 and 54.57 ± 5.84, respectively) (p < .05). In preventive protocols, the RPA extract significantly reduced urinary and renal oxalate levels and increased urinary calcium and citrate levels compared to the control. In addition, the RPA preventive protocol significantly decreased osteopontin expression, renal crystallization, and pathological changes compared to the control. These changes were not observed in rats on the therapeutic protocol. CONCLUSIONS: RPA is a useful agent that prevents the formation of CaOx kidney stones.

Effect of external phosphate addition on solid-phase iron distribution and iron accumulation in Mangrove Kandelia obovata (S. L.).

In this study, a pot experiment was conducted to evaluate the effect of phosphate (PO4 (3-)) addition on iron (Fe) cycling in mangrove ecosystem. Kandelia obovata (S. L.), one of the dominant mangrove species in the southeast of China, was cultivated in rhizoboxes under three different levels of P concentrations. Results showed the solid-phase Fe distribution and Fe(II)/Fe(III) values in both the root zone (rhizosphere) and bulk soil (non-rhizosphere) were comparable among all P levels (p > 0.05); P addition significantly decreased the pore water Fe content both in the rhizosphere and non-rhizosphere zone (p < 0.05); higher amount of reactive Fe was found in rhizosphere sediments, while in the non-rhizosphere sediments, higher concentration of crystalline Fe was determined; P significantly increased iron plaque formation and iron accumulation in K. obovata (S. L.) tissues (p < 0.05); P addition increased K. obovata (S. L.) biomass and chlorophyll content. It was suggested that P is implicated in the Fe cycling in mangrove plants; more reactive iron, higher abundance of root Fe-reducing bacteria (FeRB) and Fe-oxidizing bacteria (FeOB), and together with higher amount of K. obovata (S. L.) root organic acids exudation result in a rapid Fe cycling in rhizosphere, which contribute to comparable solid-phase iron distribution among different P levels.

Interactive effects of cadmium and pyrene on contaminant removal from co-contaminated sediment planted with mangrove Kandelia obovata (S., L.) Yong seedlings.

The interactive effects of cadmium (Cd) and pyrene (Pyr) on contaminant removal from co-contaminated sediment planted with Kandelia obovata were investigated by a pot experiment. We found that dry weight of plant was significantly decreased under high level of Cd-Pyr combined stress. High Pyr caused the increase of Cd toxicity to K. obovata under high Cd stress because more Cd translocated to the plant tissues. Cd toxicity inhibited Pyr degradation in co-contaminated sediments and higher Pyr degradation was found in the rhizosphere than that in the non-rhizosphere sediment under high Cd treatment. The total number of microorganisms in sediments tended to decrease with increasing Cd under Cd-Pyr combined stress and more amount existed in the rhizosphere sediment. In conclusion, Cd and Pyr removal by K. obovata can influence interactions between these two pollutants in co-contaminated sediment. This suggests that this mangrove can effectively remedy sites co-contaminated with these two types of contamination.

Silicon alleviates cadmium toxicity in Avicennia marina (Forsk.) Vierh. seedlings in relation to root anatomy and radial oxygen loss.

The effects of Si on growth, the anatomy of the roots, radial oxygen loss (ROL) and Fe/Mn plaque on the root surface were investigated in Avicennia marina (Forsk.) Vierh. seedlings under Cd stress. Si prompted the growth of seedlings and reduced the Cd concentration in the root, stem and leaf of A. marina. Si prompted the development of the apoplastic barrier in the roots, which may be related to the reduction of Cd uptake. The higher amount of ROL and Mn plaque on the root surface due to Si were also related to the promotion of Cd tolerance in A. marina seedlings. Therefore, it is concluded that the alteration of the anatomy of the roots, the increase of ROL and Mn plaque of A. marina seedlings play an important role in alleviation of Cd toxicity due to Si.