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The phosphorylation of synaptic proteins is a significant biochemical reaction that controls the sleep–wake cycle in mammals1, 2–3. Protein phosphorylation in vivo is reversibly regulated by kinases and phosphatases. In this study, we investigate a pair of kinases and phosphatases that reciprocally regulate sleep duration. First, we perform a comprehensive screen of protein kinase A (PKA) and phosphoprotein phosphatase (PPP) family genes by generating 40 gene knockout mouse lines using prenatal and postnatal CRISPR targeting. We identify a regulatory subunit of PKA (Prkar2b), a regulatory subunit of protein phosphatase 1 (PP1; Pppr1r9b) and catalytic and regulatory subunits of calcineurin (also known as PP2B) (Ppp3caand Ppp3r1) as sleep control genes. Using adeno-associated virus (AAV)-mediated stimulation of PKA and PP1–calcineurin activities, we show that PKA is a wake-promoting kinase, whereas PP1 and calcineurin function as sleep-promoting phosphatases. The importance of these phosphatases in sleep regulation is supported by the marked changes in sleep duration associated with their increased and decreased activities, ranging from approximately 17.3 h per day (PP1 expression) to 4.3 h per day (postnatal CRISPR targeting of calcineurin). Localization signals to the excitatory post-synapse are necessary for these phosphatases to exert their sleep-promoting effects. Furthermore, the wake-promoting effect of PKA localized to the excitatory post-synapse negated the sleep-promoting effect of PP1–calcineurin. These findings indicate that PKA and PP1–calcineurin have competing functions in sleep regulation at excitatory post-synapses.

Developing highly efficient Pt-based methanol oxidation reaction (MOR) catalysts is pivotal for direct methanol fuel cells. Phase engineering of nanomaterials offers a promising strategy to improve their catalytic performance, yet achieving phase modulation in one-dimensional nanowires (NWs) remains a great challenge. Herein, we report a facile and one-pot synthesis approach for the crystal-phase-controlled Pt-Sn intermetallic nanowires (NWs), realizing the crystal-phases regulation of face-centered cubic Pt3Sn intermetallic NWs (FCC-Pt3Sn INTNWs) and hexagonal close-packed PtSn intermetallic NWs (HCP-PtSn INTNWs) by adjusting the amounts of Sn precursors. Notably, the FCC-Pt3Sn INTNWs exhibit high mass and specific activities of 6.4 A mgPt-1and 11.8 mA cm-2, respectively, surpassing its counterparts, the HCP-PtSn INTNWs and commercial Pt/C catalysts. After a 10,000 s durability test, the FCC-Pt3Sn INTNWs still maintain a mass activity of 5.6 A mgPt-1, which is 24.3 times higher than that of commercial Pt/C catalyst. This dramatic enhancement of MOR performance is primarily attributed to the phasecontrolled structure and accelerated removal of CO intermediates (CO*). Theoretical calculations and CO stripping experiments demonstrate that the FCC-Pt3Sn INTNWs lower the energy barrier for converting CO* into COOH* by reducing CO* binding and enhancing OH adsorption, thus significantly improving the MOR activity, CO tolerance, and stability.

Circulating tumor cells (CTCs) are the “seeds” for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and treatment.

Here, we report low-voltage-driven fast-response nanostructured columnar ionic liquid crystal/polymer composite actuators that form three-dimensional continuous ion channels. A three-component self-assembly of a zwitterionic rod-like molecule (49.5 wt %), an ionic liquid (27.5 wt %), and poly(vinyl alcohol) (23.0 wt %) provided a free-standing stretchable membrane electrolyte. The dissociated ions can move through a continuous 3D ionophilic matrix surrounding the hydrophobic columns formed by the hexagonally organized rod-mesogens. Three-layer actuators composed of the electrolyte film sandwiched between two conductive polymer film electrodes of doped polythiophene exhibited a bending motion with 0.32% strain and moved 2 mm within 220 ms under 1 V at 0.1 Hz in 70% relative humidity due to the formation of electric double layers at the soft solid electrolyte/electrode interfaces. The bending strain of the columnar nanostructured actuator is comparable to those of polymer iongel actuators and block polymer actuators containing 25–80 wt % of ionic liquids. It is noteworthy that a small number of ions organized into the 3D nanochannels can generate the large bending deformation, which can contribute to reduce the risk of leakage of ions and the production cost. In addition, we have demonstrated a low-voltage-driven deformable mirror actuator that is expected to be applied to optical devices.

The demand for highly permeable and selective thin-film composite (TFC) nanofiltration membranes, which are essential for seawater and brackish water softening and resource recovery, is growing rapidly. However, improving and tuning membrane permeability and selectivity simultaneously remain highly challenging owing to the lack of thickness control in polyamide films. In this study, we fabricated a high-performance interlayered TFC membrane through classical interfacial polymerization on a MoS2-coated polyethersulfone substrate. Due to the enhanced confinement effect on the interface degassing and the improved adsorption of the amine monomer by the MoS2interlayer, the MoS2-interlayered TFC membrane exhibited enhanced roughness and crosslinking. Compared to the control TFC membrane, MoS2-interlayered TFC membranes have a thinner polyamide layer, with thickness ranging from 60 to 85 nm, which can be tuned by altering the MoS2interlayer thickness. A multilayer permeation model was developed to delineate and analyze the transport resistance and permeability of the MoS2interlayer and polyamide film through the regression of experimental data. The optimized MoS2-interlayered TFC membrane (0.3-inter) had a 96.8% Na2SO4rejection combined with an excellent permeability of 15.9 L m–2h–1bar–1(LMH/bar), approximately 2.4 times that of the control membrane (6.6 LMH/bar). This research provides a feasible strategy for the rational design of tunable, high-performance NF membranes for environmental applications.

Amyloid fibrillation by hen egg white lysozyme (HEWL) under the influences of two common surfactants, sodium dodecyl sulfate (SDS) and Triton X-100 (TX-100), was investigated with atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. Detailed AFM investigations indicated that both SDS and TX-100 were able to induce some significant morphological changes of HEWL amyloid fibrils. Both SDS and TX-100 could induce a morphological change which was characterized with alternating fibril regions with increased thicknesses along the fibril axis. In addition, TX-100 was also able to induce a morphological change which was characterized with fibril branching. In contrast, the positively charged cetyltrimethylammonium bromide displayed no such effect as compared with the negatively charged SDS and the nonionic TX-100. These intriguing modulation effects of SDS and TX-100 on amyloid fibrillation were hypothesized to be due to surfactant-induced surface-catalyzed secondary nucleation owing to the noncovalent interaction between the surfactants and HEWL. The proposed hypothesis was further supported by FTIR spectroscopic investigation, which demonstrated the formation of a SDS–amyloid fibril complex and TX-100–amyloid fibril complex. Detailed FTIR analysis suggested that the tail group of SDS associated with amyloid fibrils is more disordered similar to that of SDS in aqueous solution, while the headgroup of SDS appears to interact with amyloid fibrils strongly similar to that of SDS in the solid state, and the ether groups of TX-100 associated with amyloid fibrils experienced a different microenvironment as compared with that of neat TX-100. Additional control experiments with FTIR spectroscopy revealed that the interactions of SDS/TX-100 with HEWL amyloid fibrils were different from those of SDS/TX-100 with HEWL amorphous aggregates. In addition, the β-sheet structures of the HEWL amyloid fibrils were found to be increased due to the influences of SDS and TX-100. Our work provides new insight into the modulation effects of surfactants on amyloid fibrillation.

Thin-film nanocomposite (TFN) membranes have garnered considerable attention for their potential to improve separation performance by incorporating nanomaterials. However, challenges such as these materials' uneven distribution and aggregation have hindered practical applications. While prior studies have largely concentrated on modifying nanosheets for compatibility with polymer matrices, the role of substrate pore size in influencing nanosheet distribution has been overlooked. In this work, MoS2nanosheets were dispersed in an aqueous phase to fabricate TFN membranes, investigating the effect of substrate pore size relative to the nanosheets. By systematically varying the particle size of MoS2and the pore size of the substrate, we reveal how these factors impact material distribution and structural uniformity within the membranes. Our findings reveal that larger substrate pores allow the MoS2-containing monomer solution to infiltrate more effectively, minimizing nanosheet aggregation. This enhances membrane performance by promoting better dispersion. Our results underscore the importance of considering the relative size of substrate pores and nanosheets in TFN membrane design, providing a pathway to improved material integration and higher membrane efficiency.

The vertical centrifugal pump is a commonly utilized unit in seawater-pumped storage hydropower plants. The volute, a crucial part of the pump, directly influences the hydraulic characteristics, stability, and efficiency. The effect of single- and double-voluted configurations on a vertical centrifugal pump is studied using the SAS (Scale Adaptation Simulation) turbulence model in this study. The validity of the computation procedure is confirmed when compared to the test results. An investigation into the pressure pulsation and the radial force is carried out. The findings indicate that different volute types do not have appreciable effects on pump efficiency or head, and the variance is less than 2 %. However, the volute design greatly affects the pressure pulsation of the casing. At three typical working conditions (0.6Q, 1.0Qand 1.1Q), the main frequency amplitude at the first tongue of the double volute is reduced by 70 %, 38 % and 40 % compared with the corresponding single volute. At the outlet of the double volute, it is 31 %, 18 %, and 22 % lower when compared to a typical single volute. The type of volute used in the pump influences the pressure distribution as well as the pressure pulsation characteristics. As the double volute adopts the diaphragm structure, its radial impeller force is smaller. When comparing single and double volute pumps, the latter has a smaller radial impeller force. Therefore, it is advised to utilize a vertical centrifugal pump with a double-volute structure. This paper provides valuable insights for selecting units for seawater-pumped storage hydropower plants.

Background: Peripheral vascular catheters (PVC) are the most frequently used invasive medical devices in hospitals, with 330 million sold each year in the USA alone. One in three UK inpatients at any one time has at least one PVC in situaccording to the Scottish National Prevalence survey.Method: A narrative review of studies describing the infection risks associated with PVCs.Results: It is estimated that 30–80% of hospitalised patients receive at least one PVC during their hospital stay. Despite their prevalence, PVCs are not benign devices, and the high number of PVCs inserted annually has resulted in serious catheter-related bloodstream infections and significant morbidity, prolonged hospital stay and increased healthcare system costs. To date, PVC infections have been under-evaluated. Most studies focus on central venous catheter rather than PVC-associated bloodstream infections. Risks associated with PVC infection must be addressed to reduce patient morbidity and associated costs of prolonged hospital admission and treatment.Discussion: This article discusses the sources and routes of PVC-associated infection and outlines known effective prevention and intervention strategies.

Delayed cerebellar development is a hallmark of Zellweger syndrome (ZS), a severe neonatal neurodegenerative disorder. ZS is caused by mutations in PEX genes, such as PEX13, which encodes a protein required for import of proteins into the peroxisome. The molecular basis of ZS pathogenesis is not known. We have created a conditional mouse mutant with brain-restricted deficiency of PEX13 that exhibits cerebellar morphological defects. PEX13 brain mutants survive into the postnatal period, with the majority dying by 35 days, and with survival inversely related to litter size and weaning body weight. The impact on peroxisomal metabolism in the mutant brain is mixed: plasmalogen content is reduced, but very-long-chain fatty acids are normal. PEX13 brain mutants exhibit defects in reflex and motor development that correlate with impaired cerebellar fissure and cortical layer formation, granule cell migration and Purkinje cell layer development. Astrogliosis and microgliosis are prominent features of the mutant cerebellum. At the molecular level, cultured cerebellar neurons from E19 PEX13-null mice exhibit elevated levels of reactive oxygen species and mitochondrial superoxide dismutase-2 (MnSOD), and show enhanced apoptosis together with mitochondrial dysfunction. PEX13 brain mutants show increased levels of MnSOD in cerebellum. Our findings suggest that PEX13 deficiency leads to mitochondria-mediated oxidative stress, neuronal cell death and impairment of cerebellar development. Thus, PEX13-deficient mice provide a valuable animal model for investigating the molecular basis and treatment of ZS cerebellar pathology.

In this work, cucurbiturils (CBs), a class of macrocyclic supramolecules, were observed to have an interesting peroxidase-like activity, which is metal-free, substrate-specific, thermophilic, acidophilic, and insensitive to ionic strength. By coating CBs on enzyme-encapsulated zeolitic imidazolate framework-8 (ZIF-8), a composite nanozyme was constructed, which retains the catalytic ability of CBs and enzymes and makes them cascade. On addition of the substrate, i.e., the detection target, a highly efficient cascade catalysis can be launched in all the spatial directions to generate sensitive and visible signals. Convenient detection of glucose and cholesterol as models is thereby achieved. More importantly, we have also successfully constructed a composite nanozyme-based sensor array (6 × 8 wells) and thereby achieved simultaneous colorimetric analysis of multiple samples. The concept and successful practice of the construction of the unique core–shell supramolecule/biomolecule@nanomaterial architecture provide the possibility to fabricate next-generation multifunctional materials and create new applications by integrating their unique functions.

Primary multiple obturator nerve schwannomas originate from Schwann cells and are extremely rare. Patients with schwannomas are asymptomatic and a retroperitoneal schwannoma is often misdiagnosed as an adnexal mass. In the present study, we describe a 58-year-old woman in whom a right adnexal mass accompanied by endometrial polyp was found incidentally through transvaginal ultrasound. The mass was diagnosed as multiple obturator nerve schwannomas after laparoscopy. Immunohistochemical assay confirmed the schwannomas to be positive for SOX10. To our knowledge, this is the first report to demonstrate a case of multiple schwannomas originating from the obturator nerve and treated by laparoscopic resection.

Imbalance in data distribution hinders the learning performance of classifiers. To solve this problem, a popular type of methods is based on sampling (including oversampling for minority class and undersampling for majority class) so that the imbalanced data becomes relatively balanced data. However, they usually focus on one sampling technique, oversampling or undersampling. Such strategy makes the existing methods suffer from the large imbalance ratio (the majority instances size over the minority instances size). In this paper, an active learning framework is proposed to deal with imbalanced data by alternative performing important sampling (ALIS), which consists of selecting important majority-class instances and generating informative minority-class instances. In ALIS, two important sampling strategies affect each other so that the selected majority-class instances provide much clearer information in the next oversampling process, meanwhile the generated minority-class instances provide much more sufficient information for the next undersampling procedure. Extensive experiments have been conducted on real world datasets with a large range of imbalance ratio to verify ALIS. The experimental results demonstrate the superiority of ALIS in terms of several well-known evaluation metrics by comparing with the state-of-the-art methods.

As a refractory fibrosis disease, intrauterine adhesions (IUAs) is defined as fibrosis of the physiological endometrium. Although hysteroscopic adhesiolysis is widely recommended as an effective treatment, prognosis and recurrence remain poor in severe cases. Recently, stem cell therapy has been promoted as a promising treatment for IUAs. The ability of human amniotic epithelial cells (hAECs), emerging as a new candidate for stem cell therapy, to treat IUAs has not been demonstrated. To study the potential effects of hAECs on IUAs, we created an IUA rat model using mechanical injury and injected cultured primary hAECs into the rats’ uteri. Next, we observed the morphological structure of endometrial thickness and glands using hematoxylin and eosin staining, and we detected extracellular-matrix collagen deposition using Masson staining. In addition, we performed immunohistochemical staining and reverse-transcription polymerase chain reaction (RT-PCR) to investigate potential fibrosis molecules and angiogenesis factors 7 d after hAECs transplantation. Finally, we detected estrogen receptor (ER) and growth factors via RT-PCR to verify the molecular mechanism underlying cell therapy. In the IUA rat models, endometrial thickness and endometrial glands proliferated and collagen deposition decreased significantly after hAEC transplantation. We found that during the recovery of injured endometrium, the crucial fibrosis marker transforming growth factor-β (TGF-β) was regulated and angiogenesis occurred in the endometrial tissue with the up-regulation of vascular endothelial growth factor. Furthermore, hAECs were shown to promote ER expression in the endometrium and regulate the inflammatory reaction in the uterine microenvironment. In conclusion, these results demonstrated that hAEC transplantation could inhibit the progression of fibrosis and promote proliferation and angiogenesis in IUA rat models. The current study suggests hAECs as a novel stem cell candidate in the treatment of severe IUA.