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Abstract: The ion-conducting pore of potassium channels, which can open and close to regulate ion passage, was at long thought to be a one-dimensional pore structure with a water-filled central cavity. Here, we find four orifices in the KcsA potassium channel, which are perpendicular to the pore and stretch out from the cavity. Equilibrium molecular dynamics simulations show that water molecules can flow between the cavity and orifices. Targeted molecular dynamics simulations show that during the opening process, water molecules can move into the cavity through the orifices to facilitate channel gating, whereas blocking the aqueduct orifices makes the channel difficult to open. [Copyright &y& Elsevier]

The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-β from tumor cells and regulating TGF-β/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process. [ABSTRACT FROM AUTHOR]

The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate neurogenic potential and cellular diversity, we profiled single-nucleus transcriptomes in five hippocampal-entorhinal subregions in humans, macaques, and pigs. Integrated cross-species analysis revealed robust transcriptomic and histologic signatures of neurogenesis in the adult mouse, pig, and macaque but not humans. Doublecortin (DCX), a widely accepted marker of newly generated granule cells, was detected in diverse human neurons, but it did not define immature neuron populations. To explore species differences in cellular diversity and implications for disease, we characterized subregion-specific, transcriptomically defined cell types and transitional changes from the three-layered archicortex to the six-layered neocortex. Notably, METTL7B defined subregion-specific excitatory neurons and astrocytes in primates, associated with endoplasmic reticulum and lipid droplet proteins, including Alzheimer's disease-related proteins. This resource reveals cell-type- and species-specific properties shaping hippocampal-entorhinal neurogenesis and function. [Display omitted] • Single-nucleus RNA-seq of adult hippocampal-entorhinal cells in human, monkey, and pig • Transcriptomic signatures of adult neurogenesis in mouse, pig, and monkey but not human • Excitatory neuron diversification delineates transitions from 3- to 6-layered cortex • METTL7B defines subregion-specific excitatory neurons and astrocytes in primates Using snRNA-seq of the adult human, macaque, and pig hippocampal-entorhinal system, Franjic et al. defined shared and divergent cell type features, like primate-specific expression of METTL7B in some excitatory neurons and astrocytes. They also identified robust transcriptomic and histologic signatures of neurogenesis in the mouse, pig, and macaque but not humans. [ABSTRACT FROM AUTHOR]

Spin‐controlled vortex generation and spin‐Hall effect, two distinct effects discovered in optics, have been extensively studied recently. However, while physical origins of two effects are both due to spin‐orbit interactions, their inherent connections remain obscure which also hinders further explorations on the manipulations of them. Here, in studying the scattering of a spin‐polarized light beam at sharp interfaces, an intriguing phase transition between vortex generation and spin‐Hall shift trigged by varying the incidence angle is revealed. After reflection/refraction, the beam contains two components: normal and abnormal modes acquiring spin‐redirection‐Berry phases and Pancharatnam–Berry phases, respectively. Inside the abnormal beam, two classes of wave components gain Pancharatnam–Berry phases with distinct topological natures, generating intrinsic and extrinsic orbital angular momenta (OAM), respectively. Enlarging incidence angle changes the relative portions of these two contributions, making the abnormal beam undergo a phase transition from vortex generation to spin‐Hall shift. Such intriguing effect is experimentally observed at a purposely designed metamaterial slab, exhibiting efficiency enhanced by several‐thousand times compared to that at a conventional slab. These findings unify two previously discovered effects in a single framework, reinterpret previous results with clearer pictures, and shed light on understanding other physical effects involving the competition between intrinsic and extrinsic OAM. [ABSTRACT FROM AUTHOR]

Dry spices are at risk of microbial contamination because traditional drying processes fail to eliminate unwanted microorganisms. Radiofrequency (RF) has shown the potential for pasteurizing agricultural products. To control the natural microflora, we added a decontamination step before hot-air drying for preparing Sichuan pepper. Sichuan pepper kernels were heated by RF to 50 °C (cold spot), held for 10 min, and dried in a hot-air convection oven at 50 °C for 10 h. The total plate counts (TPCs) and quality loss were traced and compared with those following a 50 °C hot-air drying process as the control group. RF heating and holding processes achieved reductions of 0.68 ± 0.52 and 1.63 ± 0.35 log CFU/g (dry base, d.b), respectively, in Sichuan pepper TPCs. The final products treated by RF had 2.45 ± 0.19 log CFU/g (d.b), whereas the TPC in the control group remained as high as 2.95 ± 0.20 log CFU/g (d.b). Sichuan pepper kernels in the two groups showed similar drying rates; however, RF-treated Sichuan pepper lost most of its oil droplets, resulting in significant reductions in flavor and color. The results indicated that RF-assisted hot-air drying could efficiently control the natural microflora of Sichuan pepper, but with severe quality deterioration. • Radiofrequency (RF) heats Sichuan pepper kernels rapidly and uniformly. • The TPC of Sichuan pepper reduced significantly after RF-assisted drying. • RF-assisted hot-air drying controlled natural microflora in Sichuan pepper. • RF treatment significantly reduced flavor and color and led to oil droplet loss. • Loss of oil droplets could affect decontamination efficacy of RF treatment. [ABSTRACT FROM AUTHOR]

Diacylglycerol kinase (DgkA) is a small integral membrane protein, responsible for the ATP-dependent phosphorylation of diacylglycerol to phosphatidic acid. Its structures reported in previous studies, determined in detergent micelles by solution NMR and in monoolein cubic phase by X-ray crystallography, differ significantly. These differences point to the need to validate these detergent-based structures in phospholipid bilayers. Here, we present a well-defined homo-trimeric structure of DgkA in phospholipid bilayers determined by magic angle spinning solid-state NMR (ssNMR) spectroscopy, using an approach combining intra-, inter-molecular paramagnetic relaxation enhancement (PRE)-derived distance restraints and CS-Rosetta calculations. The DgkA structure determined in lipid bilayers is different from the solution NMR structure. In addition, although ssNMR structure of DgkA shows a global folding similar to that determined by X-ray, these two structures differ in monomeric symmetry and dynamics. A comparative analysis of DgkA structures determined in three different detergent/lipid environments provides a meaningful demonstration of the influence of membrane mimetic environments on the structure and dynamics of membrane proteins. Jianping Li et al. present the homo-trimeric structure of the small integral membrane protein diacylglycerol kinase (DgkA) in phospholipid bilayers determined by magic angle spinning solid-state NMR spectroscopy. They compare the structure with structures solved by solution NMR and X-ray crystallography and provide insights into the influence of membrane mimetic environments on membrane proteins. [ABSTRACT FROM AUTHOR]

The performance of diverse types of bio-oils varies greatly from each other, which makes it arduous to apply different bio-oils directly in engineering practice. This study is based on physical and microscopic properties, studying different types of bio-oil recycled asphalt and analyzing their differences. Five bio-oils (castor oil, straw oil, soybean oil, gutter oil, and vegetable oil) were used to regenerate asphalts after short-term and long-term aging to prepare recycled asphalts. The physical performances of recycled asphalts with different bio-oils were assessed, including penetration, softening point, and ductility tests. In addition, scanning electron microscopy was utilized to investigate the microscopic morphologies of recycled asphalts. Simultaneous thermogravimetry and differential scanning calorimetry were applied to determine the thermal stabilities of recycled asphalts. Finally, Gel permeation chromatography was employed to analyze the asphalt's relative molecular masses. The results revealed that vegetable and gutter oil have apparent adverse effects on temperature sensitivity and high-temperature performance of aged asphalt. In contrast, they have positive effects on low-temperature performance. All five bio-oils can repair cracks on the surface of aged asphalt. However, the surface wrinkles of vegetable oil-recycled asphalt and castor oil-recycled asphalt are relatively less and have an outstanding recycling effect. The slight thermal weight loss of recycled asphalts corresponding to castor oil, straw oil, and soybean oil at high temperatures positively impacted the high-temperature stability of aged asphalt. The castor oil and soybean oil recycled asphalts have significantly larger relative molecular masses and have advantages in high-temperature performance. This paper reveals the impact of different bio-oils on asphalt regeneration, which contributes a theoretical basis for promoting the practical implementation of bio-oil in road projects, with obvious economic and social benefits. • Five different bio-oils were used as recycling agents for aged asphalt. • The physical characteristics of different bio-oil recycled asphalts were studied. • The thermal stability and relative molecular mass of bio-oil recycled asphalts were analyzed. [ABSTRACT FROM AUTHOR]

Abl family kinases are evolutionarily conserved regulators of cell migration and morphogenesis. Genetic experiments in Drosophila suggest that Abl family kinases interact functionally with microtubules to regulate axon guidance and neuronal morphogenesis. Vertebrate Abl2 binds to microtubules and promotes their plus-end elongation, both in vitro and in cells, but the molecular mechanisms by which Abl2 regulates microtubule (MT) dynamics are unclear. We report here that Abl2 regulates MT assembly via condensation and direct interactions with both the MT lattice and tubulin dimers. We find that Abl2 promotes MT nucleation, which is further facilitated by the ability of the Abl2 C-terminal half to undergo liquid-liquid phase separation (LLPS) and form co-condensates with tubulin. Abl2 binds to regions adjacent to MT damage, facilitates MT repair via fresh tubulin recruitment, and increases MT rescue frequency and lifetime. Cryo-EM analyses strongly support a model in which Abl2 engages tubulin C-terminal tails along an extended MT lattice conformation at damage sites to facilitate repair via fresh tubulin recruitment. Abl2Δ688-790, which closely mimics a naturally occurring splice isoform, retains binding to the MT lattice but does not bind tubulin, promote MT nucleation, or increase rescue frequency. In COS-7 cells, MT reassembly after nocodazole treatment is greatly slowed in Abl2 knockout COS-7 cells compared with wild-type cells, and these defects are rescued by re-expression of Abl2, but not Abl2Δ688-790. We propose that Abl2 locally concentrates tubulin to promote MT nucleation and recruits it to defects in the MT lattice to enable repair and rescue. [Display omitted] • Abl2 binds tubulin dimers and undergoes LLPS • Co-condensation of Abl2 and tubulin promotes MT nucleation under LLPS conditions • Abl2 binds expanded MT lattices and bridges subunits along a protofilament • Abl2 promotes rescue and facilitates MT reassembly after nocodazole washout in cells Genetic studies suggested that Abl family kinases interact functionally with microtubules (MTs) to promote cell morphogenesis, but the underlying mechanisms were unknown. Duan, Lyu, et al. show that Abl2 recruits tubulin dimers to sites of MT lattice expansion or damage to promote MT nucleation and rescue in vitro and MT reassembly in cells. [ABSTRACT FROM AUTHOR]

Abstract In recent years, the development of multi-targeted inhibitors has captured extensive attention of research for treating of T-cell mediated autoimmune and inflammatory diseases. In this paper, three-dimensional quantitative structure-activity relationship and docking studies were performed on 41 aminopyrimidines as three-targeted Lck/Src/KDR inhibitors. The appropriate binding orientations and conformations of these compounds interacting with Lck, Src and KDR kinases were revealed by docking studies, and the established optimum CoMFA models yielded q 2 = 0.821, R 2 = 0.997 for Lck, q 2 = 0.803, R 2 = 0.998 for Src and q 2 = 0.819, R 2 = 0.997 for KDR, and the best CoMSIA models gave q 2 = 0.772, R 2 = 0.991 for Lck (SHD), q 2 = 0.866, R 2 = 0.997 for Src (SHD) and q 2 = 0.832, R 2 = 0.993 for KDR (SHA). Systemic external validations further confirm the satisfactory predictive power of these models, producing R 2 pred values of 0.836 and 0.821 for Lck, 0.837 and 0.843 for Src, and 0.828 and 0.848 for KDR, r 2 m values of 0.951 and 0.896 for Lck, 0.915 and 0.821 for Src, and 0.854 and 0.934 for KDR, respectively. Some structural factors influencing the activities of these compounds were discussed in detail. In addition, the key amino acids impacting the receptor-ligand interactions have been identified. The inhibitory activities of these compounds to inhibit isolated Lck, Src and KDR are well linearly correlated, demonstrating that similar interaction features may exist for this series of compounds. These theoretical results can offer useful references for designing novel potential three-targeted Lck/Src/KDR inhibitors. Graphical abstract Image 1 Highlights • 3D-QSAR and docking studies were performed on 41 aminopyrimidines as three-targeted Lck/Src/KDR inhibitors. • The 3D-QSAR study yielded stable and statistically significant predictive models with high q 2 and R 2 as well as small SEE. • It is interesting to find good consistency between 3D-QSAR and molecular docking analyses for this studied system. • The inhibitory activities of these compounds to inhibit isolated Lck, Src and KDR are well linearly correlated. • Key amino acids influencing the receptor-ligand interactions have been identified. [ABSTRACT FROM AUTHOR]

As a common fungicide, difenoconazole (DFZ) is widespread in the natural environment and poses many potential threats. Carp makes up a significant proportion of China's freshwater aquaculture population and are vulnerable to the DFZ. Therefore, this study investigated the effects of DFZ (0.488 mg/L and 1.953 mg/L) exposure for 4 d on the intestinal tissues of carp and explored the mechanisms. Specifically, DFZ exposure caused pathological damage to the intestinal tissues of carp, reducing the expression levels of intestinal tight junction proteins, and leading to damage to the intestinal barrier. In addition, DFZ exposure activated the NF-κB signaling pathway, increasing the levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and decreasing the levels of anti-inflammatory factors (IL-10, TGF-β1). As disruption of the intestinal barrier is closely linked to oxidative stress and apoptosis, we have conducted research in both areas for this reason. The results showed that DFZ exposure elevated reactive oxygen species in carp intestines, decreased antioxidant enzyme activity, and suppressed the expression of oxidative stress-related genes. TUNEL results showed that DFZ induced the onset of apoptosis. In addition, the expression levels of apoptosis-related genes and proteins were examined. Western blotting results showed that DFZ could upregulate the protein expression levels of Bax, Cytochrome C and downregulate the protein levels of Bcl-2. qPCR results showed that DFZ could upregulate the transcript levels of Bax, Caspase-3, Caspase-8 and Caspase-9 and downregulate the transcript levels of Bcl-2 transcript levels. This suggests that DFZ can induce apoptosis of mitochondrial pathway in carp intestine. In conclusion, DFZ can induce oxidative stress and apoptosis in carp intestine, leading to the destruction of intestinal physical barrier and the occurrence of inflammation. Our data support the idea that oxidative stress and apoptosis are important triggers of pesticide-induced inflammatory bowel illness. [Display omitted] • Difenoconazole (DFZ) disrupts the physical barrier of the intestinal tract of carp leading to inflammatory reaction. • DFZ promotes the burst of reactive oxygen species leading to oxidative stress in the intestinal tissue in carp. • DFZ induces apoptosis in carp intestine via the mitochondrial pathway. • Inflammatory bowel disease caused by DFZ is strongly associated with oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

PEG3 is a paternally imprinted gene located on chromosome 19q13.4 and one of the most common low-expression genes in human ovarian cancer. PEG3 plays an important role in p53-related cell death. However, whether PEG3 plays a role in renal clear cell carcinoma (ccRCC) remains unclear. Here, we found that PEG3 was epigenetic inactivated and played a tumor suppressor role in ccRCC. Overexpression of PEG3 inhibited ccRCC cell proliferation and colony formation, while removal of PEG3 significantly promoted cell proliferation in vitro and tumor formation in nude mice in vivo. EZH2-mediated H3K27me3 at the PEG3 promoter suppressed PEG3 expression. EZH2 specific inhibitors promote PEG3 transcriptional expression through the transition from H3K27me3 to H3K27ac at the PEG3 promoter region. Depletion of PEG3 inhibited the activation of the p53 signaling pathway, resulting in the resistance of ccRCC to EZH2 inhibitors treatment. Thus, our data show that EZH2-mediated epigenetic inactivation of PEG3 promotes the progress of ccRCC, and reactivation of PEG3 may be a promising strategy for ccRCC. • The relationship between the expression of PEG3 in clear cell renal cell carcinoma and the prognosis of patients was explored. • The role of EZH2 in cells was explored and related to the expression of PEG3, which may provide a new idea for the treatment of clear cell renal cell carcinoma. • Epigenetic reactivation of PEG3 by EZH2 inhibitors inhibits the progression of clear cell renal cell carcinoma. • The function of PEG3 was verified by cell experiments, which demonstrated that PEG3 is a tumor suppressor. [ABSTRACT FROM AUTHOR]

This paper mainly addresses the simultaneous attack of multiple missiles against a maneuvering target in three-dimensional (3-D) space. Here, we show that a novel fixed-time fast nonsingular terminal slide mode surface (FNTSMS), which has the characteristics of nonsingularity, converges in fixed time. With the help of the fixed-time FNTSMS, fixed-time adaptive distributed guidance laws along and perpendicular to the line of sight (LOS) direction are proposed. This realizes the dynamic adjustment of the target parameters in guidance laws, reduces the energy consumption of the guidance process, and realizes the constraints of the impact time and angle simultaneously. Additionally, considering that the communication topology will cause topology switching failure, this paper proves through graph theory that the proposed adaptive guidance laws will not be affected by topology switching. Moreover, through relevant auxiliary transformations, guidance laws with control input delay are demonstrated. To close to the actual action process of the missile, the air resistance item is added to guidance laws and analyzed. In addition, the control input amplitude is restricted to meet the actual working conditions of the missile. Finally, simulations are conducted to demonstrate the performance of the guidance law and its robustness against the mutation of communication topology. [ABSTRACT FROM AUTHOR]

Abstract: Eye-protection glasses against YAG laser injury based on band gap reflection of one-dimensional photonic crystal (PC) is designed and manufactured in this paper. The laser beam (wavelength 1.06μm) is reflected by the one-dimensional PC (with the transmission 10−7) and absorbed by the phosphatic glass substrate (with the transmission 1% for 1.06μm), so the transmission of the device for wavelengths of1.06μm can reach 10−9. The glasses have enough capabilities to protect the eyes from injury of ns-YAG lasers whose energy density is 1J/cm2 for all incident angles, and also to avoid a second injury to others from the reflected laser beams. The transmission of the glasses is beyond 70% for the visible lights. The testing data of the eye-protection glasses agree well with the theoretical predictions. [Copyright &y& Elsevier]

Vast quantities of multi-omic data have been produced to characterize the development and diversity of cell types in the cerebral cortex of humans and other mammals. To more fully harness the collective discovery potential of these data, we have assembled gene-level transcriptomic data from 188 published studies of neocortical development, including the transcriptomes of ~30 million single-cells, extensive spatial transcriptomic experiments and RNA sequencing of sorted cells and bulk tissues: nemoanalytics.org/landing/neocortex. Applying joint matrix decomposition (SJD) to mouse, macaque and human data in this collection, we defined transcriptome dynamics that are conserved across mammalian neurogenesis and which elucidate the evolution of outer, or basal, radial glial cells. Decomposition of adult human neocortical data identified layer-specific signatures in mature neurons and, in combination with transfer learning methods in NeMO Analytics, enabled the charting of their early developmental emergence and protracted maturation across years of postnatal life. Interrogation of data from cerebral organoids demonstrated that while broad molecular elements of in vivo development are recapitulated in vitro , many layer-specific transcriptomic programs in neuronal maturation are absent. We invite computational biologists and cell biologists without coding expertise to use NeMO Analytics in their research and to fuel it with emerging data (carlocolantuoni.org).

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here, we explored the expression dynamics of cortical and neuropsychiatric disorder-associated genes in datasets generated from human NSCs across telencephalic fate transitions in vitro and in vivo. We identified risk genes expressed in brain organizers and sequential gene regulatory networks across corticogenesis revealing disease-specific critical phases, when NSCs are more vulnerable to gene dysfunctions, and converging signaling across multiple diseases. Moreover, we simulated the impact of risk transcription factor (TF) depletions on different neural cell types spanning the developing human neocortex and observed a spatiotemporal-dependent effect for each perturbation. Finally, single-cell transcriptomics of newly generated autism-affected patient-derived NSCs in vitro revealed recurrent alterations of TFs orchestrating brain patterning and NSC lineage commitment. This work opens new perspectives to explore human brain dysfunctions at the early phases of development., Competing Interests: COMPETING INTERESTS The authors declare no conflict of interest.

Background: The micro gas chromatography column (μGCC) is one of the key components of the miniaturized gas chromatography system. However, light alkanes are difficult to be separated by a micro gas chromatography column, especially for methane and ethane, because the length of μGCC is limited by the area of a silicon substrate. More importantly, the heterogeneous microchannel surface formed by silicon glass bonding causes uneven stationary phase coating and the forces between the untreated microchannel surfaces and the stationary phase materials are weak, which will prevent the improvement of separation performance., Results: In this paper, a micro gas chromatography column (μGCC) with uniform HKUST-1 stationary phase is reported. Significantly, an alumina film prepared by the atomic layer deposition (ALD) technique is used to homogenize the heterogeneous microchannels. The alumina is a hydrophilic material and the alumina made by the ALD technique is uniform. The forces between hydrophilic alumina film and HKUST-1 are strong, which can greatly improve the coating uniformity of the hydrophilic stationary phase HKUST-1. The test results show that the μGCC could baseline separate the light alkane mixtures (CH 4 , C 2 H 6 , C 3 H 8 , and C 4 H 10 ) at the high testing temperature of 120 °C. The maximum resolution of the difficult-separated methane and ethane reached 19.2, which is 108 % higher than the μGCC using the same stationary phase without homogenizing the microchannel inner surface., Significance: The μGCC uses ALD alumina film to homogenize the microchannel inner surface; meanwhile, hydrophilic ALD alumina has a strong electrostatic attraction with the hydrophilic stationary phase HKUST-1. Homogeneous microchannel surface and strong electrostatic attraction are favorable to obtain uniform stationary phase which greatly improves the separation performance, resulting in a large resolution for methane and ethane. The μGCC has broad application prospects in light alkane separation., Competing Interests: Declaration of competing interest The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence this work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Topological photonic insulators show promise for applications in compact integrated photonic circuits due to their ability to transport light robustly through sharp bendings. The number of topological edge states relies on the difference between the bulk Chern numbers across the boundary, as dictated by the bulk edge correspondence. The interference among multiple topological edge modes in topological photonics systems may allow for controllable functionalities that are particularly desirable for constructing reconfigurable photonic devices. In this work, we demonstrate magnetically controllable multimode interference based on gyromagnetic topological photonic insulators that support two unidirectional edge modes with different dispersions. We successfully achieve controllable power splitting in experiments by engineering multimode interference with the magnetic field intensity or the frequency of wave. Our work demonstrates that manipulating the interference among multiple chiral edge modes can facilitate the advancement of highly efficient and adaptable microwave devices., (© 2024. The Author(s).)

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment., (© 2024. The Author(s).)

DNA methylation is an important mechanism for epigenetic modifications that have been shown to be associated with responses to plant development. Previous studies found that inverted Populus yunnanensis cuttings were still viable and could develop into complete plants. However, the growth status of inverted cuttings was weaker than that of upright cuttings, and the sprouting time of inverted cuttings was later than that of upright cuttings. There is currently no research on DNA methylation patterns in inverted cuttings of Populus yunnanensis . In this study, we detected genome-wide methylation patterns of stem tips of Populus yunnanensis at the early growth stage and the rapid growth stage by Oxford Nanopore Technologies (ONT) methylation sequencing. We found that the methylation levels of CpG, CHG, CHH, and 6mA were 41.34%, 33.79%, 17.27%, and 12.90%, respectively, in the genome of inverted poplar cuttings, while the methylation levels of the four methylation types were higher in the genome of upright poplar cuttings than in inverted cuttings, 41.90%, 34.57%, 18.09%, and 14.11%, suggesting important roles for DNA methylation in poplar cells. In all comparison groups, CpG-type methylation genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were annotated to pathways associated with carbon metabolism, ribosome biogenesis in eukaryotes, glycolysis/gluconeogenesis, pyruvate metabolism, and mRNA detection pathways, suggesting that different biological processes are activated in upright and inverted cuttings. The results show that methylation genes are commonly present in the poplar genome, but only a few of them are involved in the regulation of expression in the growth and development of inverted cuttings. From this, we screened the DET2 gene for significant differences in methylation levels in upright or inverted cuttings. The DET2 gene is a key gene in the Brassinolide (BRs) synthesis pathway, and BRs have an important influence on the growth and development process of plants. These results provide important clues for studying DNA methylation patterns in P. yunnanensis .

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of the BRG1-associated factor (BAF) chromatin remodelling complex, as a candidate congenital hydrocephalus gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, congenital hydrocephalus-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo. Here, we aimed to assess the prevalence of SMARCC1 variants in an expanded patient cohort, describe associated clinical and radiographic phenotypes, and assess the impact of Smarcc1 depletion in a novel Xenopus tropicalis model of congenital hydrocephalus. To do this, we performed a genetic association study using whole-exome sequencing from a cohort consisting of 2697 total ventriculomegalic trios, including patients with neurosurgically-treated congenital hydrocephalus, that total 8091 exomes collected over 7 years (2016-23). A comparison control cohort consisted of 1798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents were sourced from the Simons Simplex Collection. Enrichment and impact on protein structure were assessed in identified variants. Effects on the human fetal brain transcriptome were examined with RNA-sequencing and Smarcc1 knockdowns were generated in Xenopus and studied using optical coherence tomography imaging, in situ hybridization and immunofluorescence. SMARCC1 surpassed genome-wide significance thresholds, yielding six rare, protein-altering de novo variants localized to highly conserved residues in key functional domains. Patients exhibited hydrocephalus with aqueductal stenosis; corpus callosum abnormalities, developmental delay, and cardiac defects were also common. Xenopus knockdowns recapitulated both aqueductal stenosis and cardiac defects and were rescued by wild-type but not patient-specific variant SMARCC1. Hydrocephalic SMARCC1-variant human fetal brain and Smarcc1-variant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2. These results suggest de novo variants in SMARCC1 cause a novel human BAFopathy we term 'SMARCC1-associated developmental dysgenesis syndrome', characterized by variable presence of cerebral ventriculomegaly, aqueductal stenosis, developmental delay and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodelling complex for human brain morphogenesis and provide evidence for a 'neural stem cell' paradigm of congenital hydrocephalus pathogenesis. These results highlight utility of trio-based whole-exome sequencing for identifying pathogenic variants in sporadic congenital structural brain disorders and suggest whole-exome sequencing may be a valuable adjunct in clinical management of congenital hydrocephalus patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Mitochondrial fission process 1 ( MTFP1 ) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC., Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A . MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A . Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis., Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1 . Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05)., Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The self-assembly of proteins into curved structures plays an important role in many cellular processes. One good example of this phenomenon is observed in the septum-forming protein (SepF), which forms polymerized structures with uniform curvatures. SepF is essential for regulating the thickness of the septum during bacteria cell division. In Bacillus subtilis , SepF polymerization involves two distinct interfaces, the β-β and α-α interfaces, which define the assembly unit and contact interfaces, respectively. However, the mechanism of curvature formation in this step is not yet fully understood. In this study, we employed solid-state NMR (SSNMR) to compare the structures of cyclic wild-type SepF assemblies with linear assemblies resulting from a mutation of G137 on the β-β interface. Our results demonstrate that while the sequence differences arise from the internal assembly unit, the dramatic changes in the shape of the assemblies depend on the α-α interface between the units. We further provide atomic-level insights into how the angular variation of the α2 helix on the α-α interface affects the curvature of the assemblies, using a combination of SSNMR, cryo-electron microscopy, and simulation methods. Our findings shed light on the shape control of protein assemblies and emphasize the importance of interhelical contacts in retaining curvature., Competing Interests: Competing interests statement:The authors declare no competing interest.

A semi-packed gas chromatographic column has the advantages of high specific surface area and low column pressure. We report that the stagnation regions formed in the adjacent posts along the channel of the semi-packed columns can decrease the area and height of chromatographic peaks, which makes it difficult to detect low-concentration mixed gases. A semi-packed column with staggered elliptic cylindrical post arrays (SC-S) made using a micro-electro-mechanical system technique is presented, and the separation performance of SC-S is compared with that of a semi-packed column with aligned elliptic cylindrical post arrays (SC-A). The simulation results show that the width of stagnation regions in SC-S is 86.89% smaller than that in SC-A. The experimental results indicate that the area and height of chromatographic peaks increased as stagnation regions reduced. In the separation of the alkane mixture from C8 through C10 with 10 ppm concentration, the chromatographic peak of decane was hardly identified in SC-A while the chromatographic peak in SC-S was still clearly visible. The chromatographic peak heights of octane and nonane were increased by 65.06% and 130.00%, respectively, in SC-S. The peak areas of octane and nonane were increased by 120.45% and 168.18%, respectively.

Rosa roxburghii and Rosa sterilis, two species belonging to the Rosaceae family, are widespread in the southwest of China. These species have gained recognition for their remarkable abundance of ascorbate in their fresh fruits, making them an ideal vitamin C resource. In this study, we generated two high-quality chromosome-scale genome assemblies for R. roxburghii and R. sterilis, with genome sizes of 504 and 981.2 Mb, respectively. Notably, we present a haplotype-resolved, chromosome-scale assembly for diploid R. sterilis. Our results indicated that R. sterilis originated from the hybridization of R. roxburghii and R. longicuspis. Genome analysis revealed the absence of recent whole-genome duplications in both species and identified a series of duplicated genes that possibly contributing to the accumulation of flavonoids. We identified two genes in the ascorbate synthesis pathway, GGP and GalLDH, that show signs of positive selection, along with high expression levels of GDP-d-mannose 3', 5'-epimerase (GME) and GDP-l-galactose phosphorylase (GGP) during fruit development. Furthermore, through co-expression network analysis, we identified key hub genes (MYB5 and bZIP) that likely regulate genes in the ascorbate synthesis pathway, promoting ascorbate biosynthesis. Additionally, we observed the expansion of terpene synthase genes in these two species and tissue expression patterns, suggesting their involvement in terpenoid biosynthesis. Our research provides valuable insights into genome evolution and the molecular basis of the high concentration of ascorbate in these two Rosa species., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment., (© 2024. The Author(s).)

Comparative "omics" studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. We performed multiregional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry and then integrated these data with complementary glycotranscriptomic data. We found that, in primates, the brain N-glycome has diverged more rapidly than the underlying transcriptomic framework, providing a means for rapidly generating additional interspecies diversity. Our data suggest that brain N-glycome evolution in hominids has been characterized by an overall increase in complexity coupled with a shift toward increased usage of α(2-6)-linked N -acetylneuraminic acid. Moreover, interspecies differences in the cell type expression pattern of key glycogenes were identified, including some human-specific differences, which may underpin this evolutionary divergence. Last, by comparing the prenatal and adult human brain N-glycomes, we uncovered region-specific neurodevelopmental pathways that lead to distinct spatial N-glycosylation profiles in the mature brain.

In the quest to connect bulk topological quantum numbers to measurable parameters in real materials, current established approaches often necessitate specific conditions, limiting their applicability. Here we propose and demonstrate an approach to link the non-trivial hierarchical bulk topology to the multidimensional partition of local density of states (LDOS), denoted as the bulk-LDOS correspondence. In finite-size topologically nontrivial photonic crystals, we observe the LDOS partitioned into three distinct regions: a two-dimensional interior bulk area, a one-dimensional edge region, and zero-dimensional corner sites. Contrarily, topologically trivial cases exhibit uniform LDOS distribution across the entire two-dimensional bulk area. Our findings provide a general framework for distinguishing topological insulators and uncovering novel aspects of topological directional band-gap materials, even in the absence of in-gap states., (© 2023. The Author(s).)

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide ( GALP ) signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

Having a spiral grain is considered to be one of the most important wood properties influencing wood quality. Here, transcriptome profiles and metabolome data were analyzed in the straight grain and twist grain of Pinus yunnanensis . A total of 6644 differential expression genes were found between the straight type and the twist type. A total of 126 differentially accumulated metabolites were detected. There were 24 common differential pathways identified from the transcriptome and metabolome, and these pathways were mainly annotated in ABC transporters, arginine and proline metabolism, flavonoid biosynthesis, isoquinoline alkaloid biosynthesis, linoleic acid metabolism, phenylpropanoid, tryptophan metabolism, etc. A weighted gene coexpression network analysis showed that the lightblue4 module was significantly correlated with 2'-deoxyuridine and that transcription factors (basic leucine zipper (bZIP), homeodomain leucine zipper (HD-ZIP), basic helix-loop-helix (bHLH), p-coumarate 3-hydroxylase (C3H), and N-acetylcysteine (NAC)) play important roles in regulating 2'-deoxyuridine, which may be involved in the formation of spiral grains. Meanwhile, the signal transduction of hormones may be related to spiral grain, as previously reported. ARF7 and MKK4&#95;5 , as indoleacetic acid (IAA)- and ethylene (ET)-related receptors, may explain the contribution of plant hormones in spiral grain. This study provided useful information on spiral grain in P. yunnanensis by transcriptome and metabolome analyses and could lay the foundation for future molecular breeding.

Superlenses made of plasmonic materials and metamaterials can image features at the subdiffraction scale. However, intrinsic losses impose a serious restriction on imaging resolution, a problem that has hindered widespread applications of superlenses. Optical waves of complex frequency that exhibit a temporally attenuating behavior have been proposed to offset the intrinsic losses in superlenses through the introduction of virtual gain, but experimental realization has been lacking because of the difficulty of imaging measurements with temporal decay. In this work, we present a multifrequency approach to constructing synthetic excitation waves of complex frequency based on measurements at real frequencies. This approach allows us to implement virtual gain experimentally and observe deep-subwavelength images. Our work offers a practical solution to overcome the intrinsic losses of plasmonic systems for imaging and sensing applications.

The deubiquitinating enzyme USP14 has been established as a crucial regulator in various diseases, including tumors, neurodegenerative diseases, and metabolic diseases, through its ability to stabilize its substrate proteins. Our group has utilized proteomic techniques to identify new potential substrate proteins for USP14, however, the underlying signaling pathways regulated by USP14 remain largely unknown. Here, we demonstrate the key role of USP14 in both heme metabolism and tumor invasion by stabilizing the protein BACH1. The cellular oxidative stress response factor NRF2 regulates antioxidant protein expression through binding to the antioxidant response element (ARE). BACH1 can compete with NRF2 for ARE binding, leading to the inhibition of the expression of antioxidant genes, including HMOX-1. Activated NRF2 also inhibits the degradation of BACH1, promoting cancer cell invasion and metastasis. Our findings showed a positive correlation between USP14 expression and NRF2 expression in various cancer tissues from the TCGA database and normal tissues from the GTEx database. Furthermore, activated NRF2 was found to increase USP14 expression in ovarian cancer (OV) cells. The overexpression of USP14 was observed to inhibit HMOX1 expression, while USP14 knockdown had the opposite effect, suggesting a role for USP14 in regulating heme metabolism. The depletion of BACH1 or inhibition of heme oxygenase 1 (coded by HMOX-1) was also found to significantly impair USP14-dependent OV cell invasion. In conclusion, our results highlight the importance of the NRF2-USP14-BACH1 axis in regulating OV cell invasion and heme metabolism, providing evidence for its potential as a therapeutic target in related diseases., Competing Interests: Declaration of competing interest All authors have no conflict of interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chiral zeroth Landau levels are topologically protected bulk states. In particle physics and condensed matter physics, the chiral zeroth Landau level plays a significant role in breaking chiral symmetry and gives rise to the chiral anomaly. Previous experimental works on such chiral Landau levels are mainly based on three-dimensional Weyl degeneracies coupled with axial magnetic fields. Their realizations using two-dimensional Dirac point systems, being more promising for future applications, were never experimentally realized before. Here we propose an experimental scheme for realizing chiral Landau levels in a two-dimensional photonic system. By introducing an inhomogeneous effective mass through breaking local parity-inversion symmetries, a synthetic in-plane magnetic field is generated and coupled with the Dirac quasi-particles. Consequently, the zeroth-order chiral Landau levels can be induced, and the one-way propagation characteristics are experimentally observed. In addition, the robust transport of the chiral zeroth mode against defects in the system is also experimentally tested. Our system provides a new pathway for the realization of chiral Landau levels in two-dimensional Dirac cone systems, and may potentially be applied in device designs utilizing the chiral response and transport robustness., (© 2023. The Author(s).)

Owing to the chirality of Weyl nodes characterized by the first Chern number, a Weyl system supports one-way chiral zero modes under a magnetic field, which underlies the celebrated chiral anomaly. As a generalization of Weyl nodes from three-dimensional to five-dimensional physical systems, Yang monopoles are topological singularities carrying nonzero second-order Chern numbers c&#95;{2}=±1. Here, we couple a Yang monopole with an external gauge field using an inhomogeneous Yang monopole metamaterial and experimentally demonstrate the existence of a gapless chiral zero mode, where the judiciously designed metallic helical structures and the corresponding effective antisymmetric bianisotropic terms provide the means for controlling gauge fields in a synthetic five-dimensional space. This zeroth mode is found to originate from the coupling between the second Chern singularity and a generalized 4-form gauge field-the wedge product of the magnetic field with itself. This generalization reveals intrinsic connections between physical systems of different dimensions, while a higher-dimensional system exhibits much richer supersymmetric structures in Landau level degeneracy due to the internal degrees of freedom. Our study offers the possibility of controlling electromagnetic waves by leveraging the concept of higher-order and higher-dimensional topological phenomena.

Comparative studies of the cerebral cortex have identified various human and primate-specific changes in both local and long-range connectivity, which are thought to underlie our advanced cognitive capabilities. These changes are likely mediated by the divergence of spatiotemporal regulation of gene expression, which is particularly prominent in the prenatal and early postnatal human and non-human primate cerebral cortex. In this review, we describe recent advances in characterizing human and primate genetic and cellular innovations including identification of novel species-specific, especially human-specific, genes, gene expression patterns, and cell types. Finally, we highlight three recent studies linking these molecular changes to reorganization of cortical connectivity., Competing Interests: Conflict of interest Nothing declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)