Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

The IRE1/Xbp1 axis restores ER and tissue homeostasis perturbed by excess Notch in Drosophila.

Notch signaling controls numerous key cellular processes including cell fate determination and cell proliferation. Its malfunction has been linked to many developmental abnormalities and human disorders. Overactivation of Notch signaling is shown to be oncogenic. Retention of excess Notch protein in the endoplasmic reticulum (ER) can lead to altered Notch signaling and cell fate, but the mechanism is not well understood. In this study, we show that V5-tagged or untagged exogenous Notch is retained in the ER when overexpressed in fly tissues. Furthermore, we show that Notch retention in the ER leads to robust ER enlargement and elicits a rough eye phenotype. Gain-of-function of unfolded protein response (UPR) factors IRE1 or spliced Xbp1 (Xbp1-s) alleviates Notch accumulation in the ER, restores ER morphology and ameliorates the rough eye phenotype. Our results uncover a pivotal role of the IRE1/Xbp1 axis in regulating the detrimental effect of ER-localized excess Notch protein during development and tissue homeostasis.

Nonlinear pulse compression of a 200 mJ and 1†kW ultrafast thin-disk amplifier.

We present a high-energy laser source consisting of an ultrafast thin-disk amplifier followed by a nonlinear compression stage. At a repetition rate of 5 kHz, the drive laser provides a pulse energy of up to 200 mJ with a pulse duration below 500 fs. Nonlinear broadening is implemented inside a Herriott-type multipass cell purged with noble gas, allowing us to operate under different seeding conditions. Firstly, the nonlinear broadening of 64 mJ pulses is demonstrated in an argon-filled cell, showing a compressibility down to 32 fs. Finally, we employ helium as a nonlinear medium to increase the energy up to 200 mJ while maintaining compressibility below 50 fs. Such high-energy pulses with sub-50 fs duration hold great promise as drivers of secondary sources.

The mTORC2/AKT/VCP axis is associated with quality control of the stalled translation of poly(GR) dipeptide repeats in C9-ALS/FTD.

Expansion of G4C2 hexanucleotide repeats in the chromosome 9 ORF 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (C9-ALS/FTD). Dipeptide repeats generated by unconventional translation, especially the R-containing poly(GR), have been implicated in C9-ALS/FTD pathogenesis. Mutations in other genes, including TAR DNA-binding protein 43 KD (TDP-43), fused in sarcoma (FUS), and valosin-containing protein, have also been linked to ALS/FTD, and upregulation of amyloid precursor protein (APP) is observed at the early stage of ALS and FTD. Fundamental questions remain as to the relationships between these ALS/FTD genes and whether they converge on similar cellular pathways. Here, using biochemical, cell biological, and genetic analyses in Drosophila disease models, patient-derived fibroblasts, and mammalian cell culture, we show that mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling is activated by APP, TDP-43, and FUS and that mTORC2/AKT and its downstream target valosin-containing protein mediate the effect of APP, TDP-43, and FUS on the quality control of C9-ALS/FTD-associated poly(GR) translation. We also find that poly(GR) expression results in reduction of global translation and that the coexpression of APP, TDP-43, and FUS results in further reduction of global translation, presumably through the GCN2/eIF2α-integrated stress response pathway. Together, our results implicate mTORC2/AKT signaling and GCN2/eIF2α-integrated stress response as common signaling pathways underlying ALS/FTD pathogenesis.

A Linear-Power-Regulated Wireless Power Transfer Method for Decreasing the Heat Dissipation of Fully Implantable Microsystems.

Magnetic coupling resonance wireless power transfer can efficiently provide energy to intracranial implants under safety constraints, and is the main way to power fully implantable brain-computer interface systems. However, the existing maximum efficiency tracking wireless power transfer system is aimed at optimizing the overall system efficiency, but the efficiency of the secondary side is not optimized. Moreover, the parameters of the transmitter and the receiver change nonlinearly in the power control process, and the efficiency tracking mainly depends on wireless communication. The heat dissipation caused by the unoptimized receiver efficiency and the wireless communication delay in power control will inevitably affect neural activity and even cause damage, thus affecting the results of neuroscience research. Here, a linear-power-regulated wireless power transfer method is proposed to realize the linear change of the received power regulation and optimize the receiver efficiency, and a miniaturized linear-power-regulated wireless power transfer system is developed. With the received power control, the efficiency of the receiver is increased to more than 80%, which can significantly reduce the heating of fully implantable microsystems. The linear change of the received power regulation makes the reflected impedance in the transmitter change linearly, which will help to reduce the dependence on wireless communication and improve biological safety in received power control applications.

An Ultra-Low-Noise, Low Power and Miniaturized Dual-Channel Wireless Neural Recording Microsystem.

As the basic tools for neuroscience research, invasive neural recording devices can obtain high-resolution neuronal activity signals through electrodes connected to the subject's brain. Existing wireless neural recording devices are large in size or need external large-scale equipment for wireless power supply, which limits their application. Here, we developed an ultra-low-noise, low power and miniaturized dual-channel wireless neural recording microsystem. With the full-differential front-end structure of the dual operational amplifiers (op-amps), the noise level and power consumption are notably reduced. The hierarchical microassembly technology, which integrates wafer-level packaged op-amps and the miniaturized Bluetooth module, dramatically reduces the size of the wireless neural recording microsystem. The microsystem shows a less than 100 nV/Hz ultra-low noise level, about 10 mW low power consumption, and 9 × 7 × 5 mm3 small size. The neural recording ability was then demonstrated in saline and a chronic rat model. Because of its miniaturization, it can be applied to freely behaving small animals, such as rats. Its features of ultra-low noise and high bandwidth are conducive to low-amplitude neural signal recording, which may help advance neuroscientific discovery.

Nonlinear pulse compression of a thin-disk amplifier and contrast enhancement via nonlinear ellipse rotation.

We demonstrate pulse compressibility from 840 fs to 38 fs of 10 mJ pulses from a thin-disk amplifier at a repetition rate of 3 kHz after nonlinear broadening in a multipass cell. In addition, the temporal-intensity contrast is enhanced via nonlinear ellipse rotation of more than a factor 50 with an optical efficiency of 56%. We believe this is the first published experimental combination of multipass cell-based nonlinear compression and nonlinear ellipse rotation-based contrast enhancement preserving both pulse compressibility and beam quality.

Efficient nonlinear compression of a thin-disk oscillator to 8.5 fs at 55 W average power.

We demonstrate an efficient hybrid-scheme for nonlinear pulse compression of high-power thin-disk oscillator pulses to the sub-10 fs regime. The output of a home-built, 16 MHz, 84 W, 220 fs Yb:YAG thin-disk oscillator at 1030 nm is first compressed to 17 fs in two nonlinear multipass cells. In a third stage, based on multiple thin sapphire plates, further compression to 8.5 fs with 55 W output power and an overall optical efficiency of 65% is achieved. Ultrabroadband mid-infrared pulses covering the spectral range 2.4-8µm were generated from these compressed pulses by intra-pulse difference frequency generation.

HTsort: Enabling Fast and Accurate Spike Sorting on Multi-Electrode Arrays.

Spike sorting is used to classify the spikes (action potentials acquired by physiological electrodes), aiming to identify their respective firing units. Now it has been developed to classify the spikes recorded by multi-electrode arrays (MEAs), with the improvement of micro-electrode technology. However, how to improve classification accuracy and maintain low time complexity simultaneously becomes a difficulty. A fast and accurate spike sorting approach named HTsort is proposed for high-density multi-electrode arrays in this paper. Several improvements have been introduced to the traditional pipeline that is composed of threshold detection and clustering method. First, the divide-and-conquer method is employed to utilize electrode spatial information to achieve pre-clustering. Second, the clustering method HDBSCAN (hierarchical density-based spatial clustering of applications with noise) is used to classify spikes and detect overlapping events (multiple spikes firing simultaneously). Third, the template merging method is used to merge redundant exported templates according to the template similarity and the spatial distribution of electrodes. Finally, the template matching method is used to resolve overlapping events. Our approach is validated on simulation data constructed by ourselves and publicly available data and compared to other state-of-the-art spike sorters. We found that the proposed HTsort has a more favorable trade-off between accuracy and time consumption. Compared with MountainSort and SpykingCircus, the time consumption is reduced by at least 40% when the number of electrodes is 64 and below. Compared with HerdingSpikes, the classification accuracy can typically improve by more than 10%. Meanwhile, HTsort exhibits stronger robustness against background noise than other sorters. Our more sophisticated spike sorter would facilitate neurophysiologists to complete spike sorting more quickly and accurately.

Multi-octave, CEP-stable source for high-energy field synthesis.

The development of high-energy, high-power, multi-octave light transients is currently the subject of intense research driven by emerging applications in attosecond spectroscopy and coherent control. We report on a phase-stable, multi-octave source based on a Yb:YAG amplifier for light transient generation. We demonstrate the amplification of a two-octave spectrum to 25 µJ of energy in two broadband amplification channels and their temporal compression to 6 and 18 fs at 1 and 2 µm, respectively. In this scheme, due to the intrinsic temporal synchronization between the pump and seed pulses, the temporal jitter is restricted to long-term drift. We show that the intrinsic stability of the synthesizer allows subcycle detection of an electric field at 0.15 PHz. The complex electric field of the 0.15-PHz pulses and their free induction decay after interaction with water molecules are resolved by electro-optic sampling over 2 ps. The scheme is scalable in peak and average power.

Carrier-envelope phase stable, 5.4 µJ, broadband, mid-infrared pulse generation from a 1-ps, Yb:YAG thin-disk laser.

We report on a simple scheme to generate broadband, µJ pulses centered at 2.1 µm with an intrinsic carrier-envelope phase (CEP) stability from the output of a Yb:YAG regenerative amplifier delivering 1-ps pulses with randomly varying CEP. To the best of our knowledge, the reported system has the highest optical-to-optical efficiency for converting 1-ps, 1 µm pulses to CEP stable, broadband, 2.1 µm pulses. The generated coherent light carries an energy of 5.4 µJ, at 5 kHz repetition rate, that can be scaled to higher energy or power by using a suitable front end, if required. The system is ideally suited for seeding broadband parametric amplifiers and multichannel synthesizers pumped by picosecond Yb-doped amplifiers, obviating the need for active timing synchronization. Alternatively, this scheme can be combined with high-power oscillators with tens of µJ energy to generate CEP stable, multioctave supercontinua, suitable for field-resolved and time-resolved spectroscopy.

Cross-polarized, multi-octave supercontinuum generation.

The generation of superoctave spectra from the interaction of intense ultrashort optical pulses and cubic nonlinearity is the result of interplay between the dispersion and nonlinearity of a material and various propagation effects. The cubic nonlinearity can be enhanced when it is combined with a quadratic-cascaded nonlinearity, relaxing the requirement on the laser's peak intensity for supercontinuum (SC) generation. In this Letter, we demonstrate and compare the generation of an SC driven from cubic and cascaded quadratic nonlinearities at an anomalous and zero dispersion wavelength (ZDW). We show the filament-free SC generation of femtosecond mid-infrared pulses by harvesting cascaded quadratic nonlinearity and, at ZDW, requires a lower threshold peak intensity and results in a higher power spectral density for the newly generated spectral components. The presented method is a suitable approach for generating multi-octave spectra from low peak-power, high average-power oscillators or a suitable seed for optical parametric amplifiers and multi-octave field synthesizers.

20 mJ, 1 ps Yb:YAG Thin-disk Regenerative Amplifier.

This is a report on a 100 W, 20 mJ, 1 ps Yb:YAG thin-disk regenerative amplifier. A homemade Yb:YAG thin-disk, Kerr-lens mode-locked oscillator with turn-key performance and microjoule-level pulse energy is used to seed the regenerative chirped-pulse amplifier. The amplifier is placed in airtight housing. It operates at room temperature and exhibits stable operation at a 5 kHz repetition rate, with a pulse-to-pulse stability less than 1%. By employing a 1.5 mm-thick beta barium borate crystal, the frequency of the laser output is doubled to 515 nm, with an average power of 70 W, which corresponds to an optical-to-optical efficiency of 70%. This superior performance makes the system an attractive pump source for optical parametric chirped-pulse amplifiers in the near-infrared and mid-infrared spectral range. Combining the turn-key performance and the superior stability of the regenerative amplifier, the system facilitates the generation of a broadband, CEP-stable seed. Providing the seed and pump of the optical parametric chirped-pulse amplification (OPCPA) from one laser source eliminates the demand of active temporal synchronization between these pulses. This work presents a detailed guide to set up and operate a Yb:YAG thin-disk regenerative amplifier, based on chirped-pulse amplification (CPA), as a pump source for an optical parametric chirped-pulse amplifier.

Near-PHz-bandwidth, phase-stable continua generated from a Yb:YAG thin-disk amplifier.

We report on the generation of a multi-octave, phase-stable continuum from the output of a Yb:YAG regenerative amplifier delivering 1-ps pulses with randomly varying carrier-envelope phase (CEP). The intrinsically CEP-stable spectral continuum spans from 450 nm to beyond 2500 nm, covering a spectral range of about 0.6 PHz. The generated coherent broadband light carries an energy of 4 µJ, which can be scaled to higher values if required. The system has been designed and is ideally suited for seeding broadband parametric amplifiers and multichannel synthesizers pumped by picosecond Yb:YAG amplifiers, obviating the need for active timing synchronization required in previous approaches. The presented concept paves the way to cost-effective, reliable all-Yb:YAG single-cycle sources with terawatt peak-power and tens-of-Watts average power.

Self-compressed, spectral broadening of a Yb:YAG thin-disk amplifier.

We demonstrate pulse shortening of 1-ps Yb:YAG thin-disk regenerative amplifier to 500 fs by cross-polarized wave generation (XPW) in a 6 mm BaF2 crystal. The process is self-compressed and has 8.5% conversion efficiency corresponding to 18 µJ energy. Our theoretical and experimental investigation shows that the factor of 3 spectral broadening and pulse shortening in ps-XPW-generation only happens in unsaturated regime. We demonstrate that the initial spectral chirp affects the spectral broadening and pulse shortening of XPW pulses.

High-power, 1-ps, all-Yb:YAG thin-disk regenerative amplifier.

We report a 100 W, 20 mJ, 1-ps, all-Yb:YAG thin-disk regenerative amplifier seeded by a microjoule-level Yb:YAG thin-disk Kerr-lens mode-locked oscillator. The regenerative amplifier is implemented in a chirped pulse amplification system and operates at an ambient temperature in air, delivering ultrastable output pulses at a 5 kHz repetition rate and with a root mean square power noise value of less than 0.5%. Second harmonic generation of the amplifier's output in a 1.5 mm-thick BBO crystal results in more than 70 W at 515 nm, making the system an attractive source for pumping optical parametric chirped pulse amplifiers in the visible and near-infrared spectral ranges.

Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer.

Sonic hedgehog (Shh), a ligand of Hedgehog signaling pathway, is considered an important oncogene and an exciting potential therapeutic target in several cancers. Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function. We and others previously demonstrated that nuclear factor-kappa B (NF-κB) activation and promoter hypomethylation contributed to the overexpression of Shh. However, the relationship between transcriptional and epigenetic regulation of Shh, and their roles in the malignant phenotype of cancer cells are still not clearly elucidated. In the present study, our data showed that the level of Shh was higher in breast cancer tissues with positive NF-κB nuclear staining and promoter hypomethylation. In addition, survival analysis revealed that Shh overexpression, but not hypomethylation and NF-κB nuclear staining, was a poor prognosis indicator for breast cancers. Moreover, in vitro data demonstrated that both NF-κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh. Mechanistically, the hypomethylation in Shh promoter could facilitate NF-κB binding to its site, and subsequently cooperate to induce transcription of Shh. Furthermore, the biological function data indicated that overexpressed Shh enhanced the self-renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF-κB activation. Overall, our findings reveal multiple and cooperative mechanisms of Shh upregulation in cancer cells, and the roles of Shh in tumor malignant behavior, thus suggesting a new strategy for therapeutic interventions to reduce Shh in tumors and improve patients' prognosis.

Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway.

We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and FEV(1) by 15% or 6 weeks elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target, whereas 12 subjects did not. The number of eosinophils in bronchial biopsies was increased by glucocorticoid withdrawal in both groups, but increases in airway T cells were found in only those with exacerbation. T-cell accumulation was a reflection of similar increases in both CD4(+) and CD8(+) T cells and was accompanied by increased expression of chemokine CCL5 (regulated upon activation, normal T cell expressed and secreted) in the airway epithelium without activation of the transcription factor nuclear factor-kappaB. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an antiviral response than an eosinophil-predominant response to allergen and implies an independent role for airway T cells in mediating asthma flares and in determining glucocorticoid efficacy in the treatment of this disease.