Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain.

Proteins of the Rbfox family act with a complex of proteins called the Large Assembly of Splicing Regulators (LASR). We find that Rbfox interacts with LASR via its C-terminal domain (CTD), and this domain is essential for its splicing activity. In addition to LASR recruitment, a low-complexity (LC) sequence within the CTD contains repeated tyrosines that mediate higher-order assembly of Rbfox/LASR and are required for splicing activation by Rbfox. This sequence spontaneously aggregates in solution to form fibrous structures and hydrogels, suggesting an assembly similar to the insoluble cellular inclusions formed by FUS and other proteins in neurologic disease. Unlike the pathological aggregates, we find that assembly of the Rbfox CTD plays an essential role in its normal splicing function. Rather than simple recruitment of individual regulators to a target exon, alternative splicing choices also depend on the higher-order assembly of these regulators within the nucleus.

Publisher Correction: A protein assembly mediates Xist localization and gene silencing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A protein assembly mediates Xist localization and gene silencing.

Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3-5 to achieve X-chromosome inactivation (XCI)6,7. The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off8. Here we show that the Xist RNA-binding proteins PTBP19, MATR310, TDP-4311 and CELF112 assemble on the multivalent E-repeat element of Xist7 and, via self-aggregation and heterotypic protein-protein interactions, form a condensate1 in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase8, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing.

Pd(0)-Catalyzed Asymmetric Cyclization/Coupling Cascade of Alkyne-Tethered Unsaturated Carbonyls: Development and Mechanism Elucidation.

While the Pd(0)-catalyzed cyclization of alkyne-tethered unsaturated carbonyl substrates has been reported, the mechanism has not been well elucidated, and the potential asymmetric version remains to be developed. Here, we disclose that a chiral Pd(0) complex can efficiently promote the desymmetrizative cyclization of alkyne-tethered cyclohexadienones in CH3OH, and the resultant Pd(II) intermediates further undergo an array of tandem coupling reactions, including Suzuki, Sonogashira, and even chemoselective reduction by CH3OH in the absence of additional coupling partners. As a result, a broad spectrum of hydrobenzofuran derivatives, having a tetra- or trisubstituted exo-alkene motif, is constructed with moderate to outstanding enantioselectivity in an exclusive cis-difunctionalization pattern. In addition, this enantioselective protocol can be well expanded to linear alkyne-tethered unsaturated carbonyls, and a new desymmetrizative and asymmetric cyclization/coupling cascade of bis-alkyne-tethered enones is further realized efficiently, furnishing diversely structured frameworks with high stereoselectivity. Moreover, kinetic transformation for various racemic alkyne-tethered enones can be accomplished under similar catalytic conditions, and unusual kinetic reactions by chemoselectively undertaking Suzuki or Sonogashira coupling, or reduction by CH3OH, occur sequentially, finally yielding two types of chiral products, both with high enantioselectivity via either ligand- or substrate-based control. The experimental results demonstrate that the current Pd(0)-based strategy is superior to the classical Pd(II)-catalyzed carbopalladation/cyclization process of the identical substrates with regard to enantioselectivity and synthetic versatility. Moreover, density functional theory calculations are conducted to rationalize the Pd(0)-catalyzed oxidative cyclometalation pathway in the key cyclization step, which leads to the observed cis-difunctionalized products exclusively.

Optical Information Transmission and Multimode Fluorescence Anticounterfeiting of Ca2-xMgxGe7O16:Mn2.

Multimode emission of Mn2+ for multimode fluorescence anticounterfeiting is achieved by cation site and interstitial occupancy in Ca2-xMgxGe7O16. The rings in Ca2-xMgxGe7O16 have a significant distortion for Mn2+ ions to enter the ring interstitials with a luminescence center at 665 nm, which is supported by XRD refinement results and first-principles calculations. The interstitial Mn2+ ion has good thermal stability with an activation energy of 0.36 eV. Surprisingly, these two luminescence centers, the cation site Mn and the interstitial Mn, have an obvious afterglow, and the disappearing afterglow will reappear by heating or irradiating with the 980 nm laser. The afterglow is significantly enhanced, as MnO2 is used as the manganese source, which is explained in detail by the thermal luminescence spectrum. Finally, Ca2-xMgxGe7O16:Mn2+ fully demonstrates its excellent prospects in fluorescent anticounterfeiting, information encryption, and optical information storage.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

1.9†µJ external-cavity dumped ultra-broad-area semiconductor nanosecond laser.

An external-cavity dumped nanosecond (ns) ultra-broad-area laser diode (UBALD) at around 966 nm with high pulse energy is demonstrated. A 1 mm UBALD is used to produce high output power and high pulse energy. A Pockels cell (PC) combines with two polarization beam splitters (PBSs) and is employed to cavity-dump a UBALD operating at 10 kHz repetition rate. At a pump current of 23 A, 11.4 ns pulses with a maximum pulse energy of ≈1.9 µJ and a maximum peak power of ≈166 W are achieved. The beam quality factor is measured to be M x 2=19.5 in the slow axis direction and M y 2=2.17 in the fast axis direction. Moreover, maximum average output power stability is confirmed, with a power fluctuation of less than 0.8% rms over 60 min. To the best of our knowledge, this is the first high-energy external-cavity dumped demonstration from an UBALD.

Multilevel synergically controlling wavefront correction of a high-power slab laser system.

We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality ß of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.

Improve the Interfacial Properties between Poly(arylene sulfide sulfone) and Carbon Fiber by Double Polymeric Grafted Layers Designed on a Carbon Fiber Surface.

Double polymeric grafted layer is constructed by two steps of chemical reaction, in which two polymers had been used, respectively polydopamine (PDA) film and modified PASS (NH2-PASS) resin containing amine group, as the interphase in carbon fiber reinforced poly(arylene sulfide sulfone) (PASS) composite (CF/PASS) to work on enhancing the interfacial property. All the test results of chemical components and chemical structures on the carbon fiber surface show that the double polymeric grafted layer was constructed successfully with PDA and NH2-PASS chains. And obvious characteristics of thin PDA film and a polymer layer can be clearly seen in the morphology of modified carbon fiber. In addition to this, the obvious interphase and change in the thickness of interphase have been observed in the modulus distribution images of CF/PASS. The final superb performance is achieved by PASS composites with a double polymeric grafted layer, 27.2% and 198.6% superior to the original PASS composite for IFSS and ILSS, respectively. Moreover, the result also indicates that constructing a double polymeric grafted layer on a carbon fiber surface is a promising technique to modify carbon fiber for processing high-performance advanced thermoplastic composites and is more environmental friendly as well as convenient.

Laparoscopic middle-hepatic-vein-guided anatomical hemihepatectomy in the treatment of hepatolithiasis: a 10-year case study.

BACKGROUND: This retrospective 10-year case study evaluated the perioperative results and long-term efficacy of laparoscopic middle-hepatic-vein-guided hemihepatectomy (L-MHV-H) and traditional anatomical hemihepatectomy (TAH) in the treatment of hepatolithiasis (HL). METHODS: From January 2010 to December 2019, 99 patients with regional HL underwent laparoscopic anatomical hemihepatectomy (LAH) at our centre, including 43 patients in the L-MHV-H group and 56 patients in the TAH group. RESULTS: All patients in both groups were Child-Pugh grade A before operation. No significant between-group differences in general information, stone distribution, comorbidities, history of previous abdominal surgery or co-occurrence of gallstones and common bile duct stones were observed. The L-MHV-H group exhibited a higher intraoperative stone clearance rate (95.3% vs. 75.0%, p = 0.014) and a lower postoperative complication rate (10.1% vs. 48.2%, p = 0.005) compared with the TAH group. In the median follow-up time of 60 months (range 6-125 months), the L-MHV-H group had lower stone recurrence (2.3% vs. 19.6%, p = 0.013) and cholangitis recurrence (2.3% vs. 17.9%, p = 0.034) rates. No significant between-group differences in the other results were observed. CONCLUSIONS: L-MHV-H is safe and feasible for HL with certain advantages over TAH in improving the intraoperative stone clearance rate, reducing postoperative complication incidence and reducing stone and cholangitis recurrence rates.

Compact integrated aberration-compensating module for a 9 kW Nd:YAG slab laser based on an off-axis stable-unstable resonator.

An integrated aberration-compensating module (IACM), consisting mainly of an adjustable slab-aberration compensator, a one-dimensional Shack-Hartmann wavefront sensor, and a data processor, which meet the urgent requirements of correcting the specific wavefront aberrations of a slab laser based on an off-axis stable-unstable resonator, is designed and experimentally demonstrated. Benefits include compactness, robustness, simplicity, automation, and cost-effectiveness. The particular wavefront aberrations of the 9 kW level quasi-continuous-wave Nd:YAG slab laser, which have characteristics of asymmetry, large amplitude and gradient, high spatial frequency, and low temporal frequency, were measured and theoretically analyzed. In the experiment, the wavefront aberrations of the slab laser were corrected by the IACM. At the average output power of 9 kW, the diffraction-limited factor ß was improved from 20.3 times diffraction limit (DL) to 3.6 times DL. The peak-to-valley and root-mean-square values of aberrations were reduced from 9.6 to 0.85 µm and from 2.86 to 0.18 µm within five iterations of the IACM, respectively. Moreover, The IACM is capable of maintaining the compensating surface figure after power-off.

Corrigendum to "Adipose-Derived Stromal Cells Attenuate Adipose Inflammation in Obesity through Adipocyte Browning and Polarization of M2 Macrophages".

[This corrects the article DOI: 10.1155/2019/1731540.].

Excellent performance of a cryogenic Nd:YAlO3 laser with low wavefront distortion based on zero thermal expansion.

High-power solid-state lasers with good beam quality are attracting great attention on account of their important applications in industry and military. However, the thermal effects generated in the laser host materials seriously limit power scaling and degrade the beam quality. Thermal lensing and thermally induced wavefront deformation are the main causes of the beam quality deterioration. Here we investigate the performance of a zero thermal expansion (ZTE) solid-state laser gain material. In a proof-of-principle experiment, an ${a}$-cut rod ${\rm Nd}\!:\!{{\rm YAlO}_3}$ (Nd:YAP) perovskite crystal is chosen to be the gain medium for ZTE around 180 K. The laser performance spanning the temperature range from 80 to 290 K is studied. The maximum output power and minimum threshold pump power were obtained at a temperature of 180 K. Moreover, the measured thermal focal power and peak-to-valley value of the wavefront distortion also reach a minimum at this temperature, an additional benefit from the crystal's ZTE coefficient. We envisage that these results will open a new route towards the development of high-power and high-beam-quality lasers through the use of ZTE gain materials.

Laparoscopic anterior hepatic transection for resecting lesions originating in the paracaval portion of the caudate lobe (with videos).

BACKGROUND: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions. METHODS: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated. RESULTS: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months. CONCLUSION: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.

Polypyrimidine tract-binding protein blocks miRNA-124 biogenesis to enforce its neuronal-specific expression in the mouse.

MicroRNA (miRNA)-124 is expressed in neurons, where it represses genes inhibitory for neuronal differentiation, including the RNA binding protein PTBP1. PTBP1 maintains nonneuronal splicing patterns of mRNAs that switch to neuronal isoforms upon neuronal differentiation. We find that primary (pri)-miR-124-1 is expressed in mouse embryonic stem cells where mature miR-124 is absent. PTBP1 binds to this precursor RNA upstream of the miRNA stem-loop to inhibit mature miR-124 expression in vivo and DROSHA cleavage of pri-miR-124-1 in vitro. This function for PTBP1 in repressing miR-124 biogenesis defines an additional regulatory loop in the already intricate interplay between these two molecules. Applying mathematical modeling to examine the dynamics of this regulation, we find that the pool of pri-miR-124 whose maturation is blocked by PTBP1 creates a robust and self-reinforcing transition in gene expression as PTBP1 is depleted during early neuronal differentiation. While interlocking regulatory loops are often found between miRNAs and transcriptional regulators, our results indicate that miRNA targeting of posttranscriptional regulators also reinforces developmental decisions. Notably, induction of neuronal differentiation observed upon PTBP1 knockdown likely results from direct derepression of miR-124, in addition to indirect effects previously described.

Recycled ancient ghost carbonate in the Pitcairn mantle plume.

The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of the isotopic mantle end members. The EM1 origin has been vigorously debated for over 25 years, with interpretations ranging from delaminated subcontinental lithosphere, to recycled lower continental crust, to recycled oceanic crust carrying ancient pelagic sediments, all of which may potentially generate the requisite radiogenic isotopic composition. Here we find that δ26Mg ratios in Pitcairn EM1 basalts are significantly lower than in normal mantle and are the lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic compositions of potentially recycled components shows that marine carbonates constitute the most common and typical reservoir invariably characterized by extremely low δ26Mg values. We therefore infer that the subnormal δ26Mg of the Pitcairn EM1 component originates from subducted marine carbonates. This, combined with previously published evidence showing exceptionally unradiogenic Pb as well as sulfur isotopes affected by mass-independent fractionation, suggests that the Pitcairn EM1 component is most likely derived from late Archean subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn lavas are inconsistent with experimental evidence showing high Ca/Al ratios in melts derived from carbonate-bearing mantle sources. We suggest that carbonate-silicate reactions in the late Archean subducted sediments exhausted the carbonates, but the isotopically light magnesium of the carbonate was incorporated in the silicates, which then entered the lower mantle and ultimately became the Pitcairn plume source.

White-light flashlight activated up-conversion luminescence for ultraviolet-B tagging.

Optical tagging technology with emission in the ultraviolet region upon visible-light excitation is promising for objects identified in visually bright environments, while the relevant research is absent. Here we put forward a covert tagging concept, which is based on up-converting phosphors (e.g., Lu3Al5O12:Pr3+) with emission peaking in the ultraviolet-B region (UV-B, 290-320 nm). A white-light flashlight serves as excitation source to make the up-converter emit, and an ultraviolet camera is applied to see such an emission wavelength range. This Letter expands the excitation source for an up-conversion process to a convenient flashlight for the first time, to the best of our knowledge. Moreover, such a flashlight-pumped UV-B tagging technology is generally applicable for many other phosphors, which can be utilized to mark and differentiate objects in commercial, civilian, or military applications.

The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China.

The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

The Non-Concentration-Quenching Phosphor Ca3Eu2B4O12 for WLED Application.

Commercial white LED devices usually suffer from a high color temperature and poor color rendering. Developing a new, efficient, and stable red phosphor is the key to solving this problem. In this work, a series of pure Ca3Y2-xB4O12:xEu3+ (0 < x ≤ 2) samples, including the new and fully transitional borate phosphor Ca3Eu2B4O12 (CEBO), have been successfully prepared by solid-state reaction synthesis. CEBO is isostructural with Ca3Y2B4O12 (CYBO), belonging to the orthorhombic system with space group Pnma (No. 62). Under optimal 393 nm excitation, this borate exhibits a strong red emission, peaking at 615 nm, with high color purity. Interestingly, the luminescence of CEBO is relatively higher than that of CYBO:Eu3+ phosphors. The quantum yield of this non-concentration-quenching phosphor reaches 95.6%. Furthermore, a warm pc-WLED device has been fabricated by mixing as-prepared CEBO powders and commercial BaMgAl10O17:Eu2+ and (Sr, Ba)2SiO4:Eu2+ phosphors, which exhibits a high color rendering index (Ra = 83.7) along with a color temperature of around 3883 K. The present work indicates that this new borate, with outstanding quantum efficiency and favorable thermal stability, can be used as a red phosphor for application in WLEDs.

Negative pressure wound therapy for patients with mediastinitis: A meta-analysis.

To evaluate clinical effects between conditional treatment and negative pressure wound therapy for mediastinal infection. Multiple databases were searched to identify relevant studies, and the articles that eventually satisfied the criteria were included. All the meta-analyses were conducted with the Review Manager 5.2. To estimate the quality of each article, risk of bias table was performed. Finally, nine studies including 648 patients met the eligibility criteria. The negative pressure wound therapy (NPWT) group and the control group included 353 and 295 patients, respectively. The meta-analysis showed no significant difference in operative time (RR = -6.13, 95%CI [-50.00, 37.74], P = .78; P for heterogeneity <.000001, I2 = 100%). The length of hospital stay (MD = -3.07, 95%CI [-4.38, -1.77], P < .00001; P for heterogeneity = .99, I2 = 0%), re-infection (RR = 0.18, 100%CI [0.08, 0.40], P < .00001; P for heterogeneity = 0.48, I2 = 0%), and mortality were significantly different between the two groups (RR = 0.27, 95%CI [0.12, 0.63], P of overall effect = .002). NPWT is a better therapy than conventional treatment for mediastinitis.