Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases.

The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Immobile polyanionic backbone enables a 900-µm-thick electrode for compact energy storage with unprecedented areal capacitance.

Thickening of electrodes is crucial for maximizing the proportion of active components and thus improving the energy density of practical energy storage cells. Nevertheless, trade-offs between electrode thickness and electrochemical performance persist because of the considerably increased ion transport resistance of thick electrodes. Herein, we propose accelerating ion transport through thick and dense electrodes by establishing an immobile polyanionic backbone within the electrode pores; and as a proof of concept, gel polyacrylic electrolytes as such a backbone are in situ synthesized for supercapacitors. During charge and discharge, protons rapidly hop among RCOO- sites for oriented transport, fundamentally reducing the effects of electrode tortuosity and polarization resulting from concentration gradients. Consequently, nearly constant ion transport resistance per unit thickness is achieved, even in the case of a 900-µm-thick dense electrode, leading to unprecedented areal capacitances of 14.85 F cm-2 at 1 mA cm-2 and 4.26 F cm-2 at 100 mA cm-2. This study provides an efficient method for accelerating ion transport through thick and dense electrodes, indicating a significant solution for achieving high energy density in energy storage devices, including but not limited to supercapacitors.

Engineering catalytic defects via molecular imprinting for high energy Li-S pouch cells.

Heterogeneous catalysis promises to accelerate sulfur-involved conversion reactions in lithium-sulfur batteries. Solid-state Li2S dissociation remains as the rate-limiting step because of the weakly matched solid-solid electrocatalysis interfaces. We propose an electrochemically molecular-imprinting strategy to have a metal sulfide (MS) catalyst with imprinted defects in positions from which the pre-implanted Li2S has been electrochemically removed. Such tailor-made defects enable the catalyst to bind exclusively to Li atoms in Li2S reactant and elongate the Li-S bond, thus decreasing the reaction energy barrier during charging. The imprinted Ni3S2 catalyst shows the best activity due to the highest defect concentration among the MS catalysts examined. The Li2S oxidation potential is substantially reduced to 2.34 V from 2.96 V for the counterpart free of imprinted vacancies, and an Ah-level pouch cell is realized with excellent cycling performance. With a lean electrolyte/sulfur ratio of 1.80 µL mgS -1, the cell achieves a benchmarkedly high energy density beyond 500 Wh kg-1.

High-Entropy Catalysis Accelerating Stepwise Sulfur Redox Reactions for Lithium-Sulfur Batteries.

Catalysis is crucial to improve redox kinetics in lithium-sulfur (Li-S) batteries. However, conventional catalysts that consist of a single metal element are incapable of accelerating stepwise sulfur redox reactions which involve 16-electron transfer and multiple Li2Sn (n = 2-8) intermediate species. To enable fast kinetics of Li-S batteries, it is proposed to use high-entropy alloy (HEA) nanocatalysts, which are demonstrated effective to adsorb lithium polysulfides and accelerate their redox kinetics. The incorporation of multiple elements (Co, Ni, Fe, Pd, and V) within HEAs greatly enhances the catalytically active sites, which not only improves the rate capability, but also elevates the cycling stability of the assembled batteries. Consequently, HEA-catalyzed Li-S batteries achieve a high capacity up to 1364 mAh g-1 at 0.1 C and experience only a slight capacity fading rate of 0.054% per cycle over 1000 cycles at 2 C, while the assembled pouch cell achieves a high specific capacity of 1192 mAh g-1. The superior performance of Li-S batteries demonstrates the effectiveness of the HEA catalysts with maximized synergistic effect for accelerating S conversion reactions, which opens a way to catalytically improving stepwise electrochemical conversion reactions.

Enhanced Oxygen Accumulation for a Hydrophobic Cathode in Lean-Oxygen Seawater Batteries.

The unsatisfactory oxygen reduction reaction (ORR) kinetics caused by the inherent lean-oxygen marine environment brings low power density for metal-dissolved oxygen seawater batteries (SWBs). In this study, we propose a seawater/electrode interfacial engineering strategy by constructing a hydrophobic coating to realize enhanced mass transfer of dissolved oxygen for the fully immersed cathode of SWBs. Accumulation of dissolved oxygen from seawater to the catalyst is particularly beneficial for improving the ORR performance under lean-oxygen conditions. As a result, SWB assembled with a hydrophobic cathode achieved a power density of up to 2.32 mW cm-2 and sustained discharge at 1.3 V for 250 h. Remarkably, even in environments with an oxygen concentration of 4 mg L-1, it can operate at a voltage approximately 100 mV higher than that of an unmodified SWB. The introduction of a hydrophobic interface enhances the discharge voltage and power of SWBs by improving interfacial oxygen mass transfer, providing new insights into improving the underwater ORR performance for practical SWBs.

PRT-Net: a progressive refinement transformer for dose prediction to guide ovarian transposition.

Introduction: Young cervical cancer patients who require ovarian transposition usually have their ovaries moved away from the pelvic radiotherapy (RT) field before radiotherapy. The dose of ovaries during radiotherapy is closely related to the location of the ovaries. To protect ovarian function and avoid ovarian dose exceeding the limits, a safe location of transposed ovary must be determined prior to surgery. Methods: For this purpose, we input the patient's preoperative CT into a neural network model to predict the dose distribution. Surgeons were able to quickly locate low-dose regions based on the dose distribution before surgery, thus determining the safe location of the transposed ovary. In this work, we proposed a new progressive refinement transformer model PRT-Net that can generate dose prediction at multiple scale resolutions in one forward propagation, and refine the dose prediction using prediction details from low to high resolution based on a deep supervision strategy. A multi-loss function fusion algorithm was also built to fit the prediction results under different loss dimensions. The clinical feasibility of the method was verified through an actual cases. Results and discussion: Therefore, using PRT-Net to predict the dose distribution by preoperative CT in cervical cancer patients can assist clinicians to perform ovarian transposition surgery and prevent patients' ovaries from exceeding the prescribed dose limit in postoperative radiotherapy.

Switching Hydrophobic Interface with Ionic Valves for Reversible Zinc Batteries.

Developing hydrophobic interface has proven effective in addressing dendrite growth and side reactions during zinc (Zn) plating in aqueous Zn batteries. However, this solution inadvertently impedes the solvation of Zn2+ with H2O and subsequent ionic transport during Zn stripping, leading to insufficient reversibility. Herein, an adaptive hydrophobic interface that can be switched "on" and "off" by ionic valves to accommodate the varying demands for interfacial H2O during both the Zn plating and stripping processes, is proposed. This concept is validated using octyltrimethyl ammonium bromide (C8TAB) as the ionic valve, which can initiatively establish and remove a hydrophobic interface in response to distinct electric-field directions during Zn plating and stripping, respectively. Consequently, the Zn anode exhibits an extended cycling life of over 2500 h with a high Coulombic efficiency of ≈99.8%. The full cells also show impressive capacity retention of over 85% after 1 000 cycles at 5 A g-1. These findings provide a new insight into interface design for aqueous metal batteries.

High yield electrosynthesis of oxygenates from CO using a relay Cu-Ag co-catalyst system.

As a sustainable alternative to fossil fuel-based manufacture of bulk oxygenates, electrochemical synthesis using CO and H2O as raw materials at ambient conditions offers immense appeal. However, the upscaling of the electrosynthesis of oxygenates encounters kinetic bottlenecks arising from the competing hydrogen evolution reaction with the selective production of ethylene. Herein, a catalytic relay system that can perform in tandem CO capture, activation, intermediate transfer and enrichment on a Cu-Ag composite catalyst is used for attaining high yield CO-to-oxygenates electrosynthesis at high current densities. The composite catalyst Cu/30Ag (molar ratio of Cu to Ag is 7:3) enables high efficiency CO-to-oxygenates conversion, attaining a maximum partial current density for oxygenates of 800 mA cm-2 at an applied current density of 1200 mA cm-2, and with 67 % selectivity. The ability to finely control the production of ethylene and oxygenates highlights the principle of efficient catalyst design based on the relay mechanism.

The complete degradation of 1,2-dichloroethane in Escherichia coli by metabolic engineering.

1,2-Dichloroethane (1,2-DCA), a widely utilized chemical intermediate and organic solvent in industry, frequently enters the environment due to accidental leaks and mishandling during application processes. Thus, the in-situ remediation of contaminated sites has become increasingly urgent. However, traditional remediation methods are inefficient and costly, while bioremediation presents a green, efficient, and non-secondary polluting alternative. In this study, an engineered strain capable of completely degrading 1,2-DCA was constructed. We introduced six exogenous genes of the 1,2-DCA degradation pathway into E. coli and confirmed their normal transcription and efficient expression in this engineered strain through qRT-PCR and proteomics. The degradation experiments showed that the strain completely degraded 2 mM 1,2-DCA within 12 h. Furthermore, the results of isotope tracing verified that the final degradation product, malic acid, entered the tricarboxylic acid cycle (TCA) of E. coli and was ultimately fully metabolized. Also, morphological changes in the engineered strain and control strain exposed to 1,2-DCA were observed under SEM, and the results revealed that the engineered strain is more tolerant to 1,2-DCA than the control strain. In conclusion, this study paved a new way for humanity to deal with the increasingly complex environmental challenges.

Pericytes in Alzheimer's disease: Key players and therapeutic targets.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that leads to progressive cognitive decline and neuropathological changes. Pericytes, which are vessel mural cells on the basement membrane of capillaries, play a crucial role in regulating cerebrovascular functions and maintaining neurovascular unit integrity. Emerging research substantiates the involvement of pericytes in AD. This review provides a comprehensive overview of pericytes, including their structure, origin, and markers and various functions within the central nervous system. Emphatically, the review explores the intricate mechanisms through which pericytes contribute to AD, including their interactions with amyloid beta and apolipoprotein E, as well as various signaling pathways. The review also highlights potential for targeted pericyte therapy for AD, with a focus on stem cell therapy and drug treatments. Future research directions include the classification of pericyte subtypes, studies related to aging, and the role of pericytes in exosome-related mechanisms in AD pathology. In conclusion, this review consolidates current knowledge on the pivotal roles of pericytes in AD and their potential as therapeutic targets, providing valuable insights for future research and clinical interventions aimed at addressing the impact of AD on patients' lives.

Both Resilience and Adhesivity Define Solid Electrolyte Interphases for a High Performance Anode.

Solid electrolyte interphases (SEIs) are sought to protect high-capacity anodes, which suffer from severe volume changes and fast degradations. The previously proposed effective SEIs were of high strength yet abhesive, inducing a yolk-shell structure to decouple the rigid SEI from the anode for accommodating the volume change. Ambivalently, the interfacial void-evolved electro-chemo-mechanical vulnerabilities become inherent defects. Here, we establish a new rationale for SEIs that resilience and adhesivity are both requirements and pioneer a design of a resilient yet adhesive SEI (re-ad-SEI), integrated into a conjugated surface bilayer structure. The re-ad-SEI and its protected particles exhibit excellent stability almost free from the thickening of SEI and the particle pulverization during cycling. More promisingly, the dynamically bonded intact SEI-anode interfaces enable a high-efficiency ion transport and provide a unique mechanical confinement effect for structural integrity of anodes. The high Coulombic efficiency (>99.8%), excellent cycling stability (500 cycles), and superior rate performance have been demonstrated in microsized Si-based anodes.

In vivo EPID-based daily treatment error identification for volumetric-modulated arc therapy in head and neck cancers with a hierarchical convolutional neural network: a feasibility study.

We proposed a deep learning approach to classify various error types in daily VMAT treatment of head and neck cancer patients based on EPID dosimetry, which could provide additional information to support clinical decisions for adaptive planning. 146 arcs from 42 head and neck patients were analyzed. Anatomical changes and setup errors were simulated in 17,820 EPID images of 99 arcs obtained from 30 patients using in-house software for model training, validation, and testing. Subsequently, 141 clinical EPID images from 47 arcs belonging to the remaining 12 patients were utilized for clinical testing. The hierarchical convolutional neural network (HCNN) model was trained to classify error types and magnitudes using EPID dose difference maps. Gamma analysis with 3%/2 mm (dose difference/distance to agreement) criteria was also performed. The F1 score, a combination of precision and recall, was utilized to evaluate the performance of the HCNN model and gamma analysis. The adaptive fractioned doses were calculated to verify the HCNN classification results. For error type identification, the overall F1 score of the HCNN model was 0.99 and 0.91 for primary type and subtype identification, respectively. For error magnitude identification, the overall F1 score in the simulation dataset was 0.96 and 0.70 for the HCNN model and gamma analysis, respectively; while the overall F1 score in the clinical dataset was 0.79 and 0.20 for the HCNN model and gamma analysis, respectively. The HCNN model-based EPID dosimetry can identify changes in patient transmission doses and distinguish the treatment error category, which could potentially provide information for head and neck cancer treatment adaption.

Consummating ion desolvation in hard carbon anodes for reversible sodium storage.

Hard carbons are emerging as the most viable anodes to support the commercialization of sodium-ion (Na-ion) batteries due to their competitive performance. However, the hard carbon anode suffers from low initial Coulombic efficiency (ICE), and the ambiguous Na-ion (Na+) storage mechanism and interfacial chemistry fail to give a reasonable interpretation. Here, we have identified the time-dependent ion pre-desolvation on the nanopore of hard carbons, which significantly affects the Na+ storage efficiency by altering the solvation structure of electrolytes. Consummating the pre-desolvation by extending the aging time, generates a highly aggregated electrolyte configuration inside the nanopore, resulting in negligible reductive decomposition of electrolytes. When applying the above insights, the hard carbon anodes achieve a high average ICE of 98.21% in the absence of any Na supplementation techniques. Therefore, the negative-to-positive capacity ratio can be reduced to 1.02 for full cells, which enables an improved energy density. The insight into hard carbons and related interphases may be extended to other battery systems and support the continued development of battery technology.

Engineering Triple-Phase Interfaces around the Anode toward Practical Alkali Metal-Air Batteries.

Alkali metal-air batteries (AMABs) promise ultrahigh gravimetric energy densities, while the inherent poor cycle stability hinders their practical application. To address this challenge, most previous efforts are devoted to advancing the air cathodes with high electrocatalytic activity. Recent studies have underlined the solid-liquid-gas triple-phase interface around the anode can play far more significant roles than previously acknowledged by the scientific community. Besides the bottlenecks of uncontrollable dendrite growth and gas evolution in conventional alkali metal batteries, the corrosive gases, intermediate oxygen species, and redox mediators in AMABs cause more severe anode corrosion and structural collapse, posing greater challenges to the stabilization of the anode triple-phase interface. This work aims to provide a timely perspective on the anode interface engineering for durable AMABs. Taking the Li-air battery as a typical example, this critical review shows the latest developed anode stabilization strategies, including formulating electrolytes to build protective interphases, fabricating advanced anodes to improve their anti-corrosion capability, and designing functional separator to shield the corrosive species. Finally, the remaining scientific and technical issues from the prospects of anode interface engineering are highlighted, particularly materials system engineering, for the practical use of AMABs.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

The impact of thermal pretreatment on phytochemical profiles and bioactivity of freeze-dried lily bulbs (Lilium lancifolium).

Lily bulbs are susceptible to deterioration during storage if improperly handled. To resolve this problem, it is necessary to investigate suitable processing techniques. The aim of this study is to evaluate the effects of steaming, blanching and microwave pretreatment on freeze-dried lily bulbs in terms of color, phenolic content and bioactivity. Results showed that appropriate steaming and blanching pretreatment could contribute to product characteristics similar to those of freeze-dried lily bulbs, with the maximum L* value reduced by only 7.57% and 0.55% respectively. Thermal pretreatment affected the retention, degradation and transformation of polyphenol, especially for regalosides. The polyphenol was closely associated with the browning of lily bulbs. Thermal processing caused the decline of regaloside A and the increase of regaloside B, which were the major phenolic monomers that can effectively inhibit the browning of lily bulbs. The antioxidant activity of freeze-dried lily pretreated with blanching for 6 min was the highest (4.39 ± 0.32 µmol TE/g DW), with an improvement of nearly 25.39% compared to that of untreated freeze-dried lily. Thus, the combination of freeze-dried with steaming or blanching pretreatment could be proposed as a sustainable strategy to improve the quality of lily bulbs for industrial application.

HDAC9-mediated calmodulin deacetylation induces memory impairment in Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. METHODS: The protein acetylation and expression levels were detected by western blotting and co-immunoprecipitation. The stoichiometry of acetylation was measured by home-made and site-specific antibodies against acetylated-CaM (Ac-CaM) at K22, K95, and K116. Hippocampus-dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. RESULTS: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+ /CaM-dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac-K22, K95-CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus-dependent memory in AD mice. CONCLUSIONS: HDAC9-mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.

Phenothiazine Derivatives as Small-Molecule Organic Cathodes with Adjustable Dropout Voltage and Cycle Performance.

Compared with conventional inorganic materials, organic electrodes are competitive candidates for secondary battery cathodes due to their resourcefulness, environmental friendliness, and cost-effectiveness. Much effort is devoted at the level of chemical structure, while ignoring the impact of molecular aggregation on battery behavior. Herein, this work designs a series of organic molecules with two electrochemically active phenothiazine groups linked by different lengths of alkyl chain to regulate molecular symmetry and crystallinity. The results emphasize the equally important role of molecular aggregation and chemical structure for battery performance. Among them, 2PTZ-C7H14|Li cell exhibits the most impressive cycle and rate performance. At the high rate of 50 C, it can still deliver a capacity of 63.4 mA h g-1 and 74.5% capacity retention after 10 000 cycles. Besides, the dropout voltage of 2PTZ-C9H18|Li cell is only 52 mV, which is among the lowest reported for lithium-organic batteries to the best of the author's knowledge.

Feasibility study of multiple-energy Bragg peak proton FLASH on a superconducting gantry with large momentum acceptance.

BACKGROUND: While the Bragg peak proton beam (BP) is capable of superior target conformity and organs-at-risk sparing than the transmission proton beam (TB), its efficacy in FLASH-RT is hindered by both a slow energy switching process and the beam current. A universal range shifter (URS) can pull back the high-energy proton beam while preserving the beam current. Meanwhile, a superconducting gantry with large momentum acceptance (LMA-SC gantry) enables fast energy switching. PURPOSE: This study explores the feasibility of multiple-energy BP FLASH-RT on the LMA-SC gantry. METHOD AND MATERIALS: A simultaneous dose and spot map optimization algorithm was developed for BP FLASH-RT treatment planning to improve the dose delivery efficiency. The URS was designed to be 0-27 cm thick, with 1 cm per step. BP plans using the URS were optimized using single-field optimization (SFO) and multiple-field optimization (MFO) for ten prostate cancer patients and ten lung cancer patients. The plan delivery parameters, dose, and dose rate metrics of BP plans were compared to those of TB plans using the parameters of the LMA-SC gantry. RESULTS: Compared to TB plans, BP plans significantly reduced MUs by 42.7% (P < 0.001) with SFO and 33.3% (P < 0.001) with MFO for prostate cases. For lung cases, the reduction in MUs was 56.8% (P < 0.001) with SFO and 36.4% (P < 0.001) with MFO. BP plans also outperformed TB plans by reducing mean normal tissue doses. BP-SFO plans achieved a reduction of 56.7% (P < 0.001) for prostate cases and 57.7% (P < 0.001) for lung cases, while BP-MFO plans achieved a reduction of 54.2% (P < 0.001) for the prostate case and 40.0% (P < 0.001) for lung cases. For both TB and BP plans, normal tissues in prostate and lung cases received 100.0% FLASH dose rate coverage (>40 Gy/s). CONCLUSIONS: By utilizing the URS and the LMA-SC gantry, it is possible to perform multiple-energy BP FLASH-RT, resulting in better normal tissue sparing, as compared to TB plans.