YWHAZ variation causes intellectual disability and global developmental delay with brain malformation.

YWHAZ encodes an adapter protein 14-3-3ζ, which is involved in many signaling pathways that control cellular proliferation, migration and differentiation. It has not been definitely correlated to any phenotype in OMIM. To investigate the role of YWHAZ gene in intellectual disability and global developmental delay, we conducted whole-exon sequencing in all of the available members from a large three-generation family and we discovered that a novel variant of the YWHAZ gene was associated with intellectual disability and global developmental delay. This variant is a missense mutation of YWHAZ, p.Lys49Asn/c.147A > T, which was found in all affected members but not found in other unaffected members. We also conducted computational modeling and knockdown/knockin with Drosophila to confirm the role of the YWHAZ variant in intellectual disability. Computational modeling showed that the binding energy was increased in the mutated protein combining with the ligand indicating that the c147A > T variation was a loss-of-function variant. Cognitive defects and mushroom body morphological abnormalities were observed in YWHAZ c.147A > T knockin flies. The YWHAZ knockdown flies also manifested serious cognitive defects with hyperactivity behaviors, which is consistent with the clinical features. Our clinical and experimental results consistently suggested that YWHAZ was a novel intellectual disability pathogenic gene.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Single-molecule optofluidic microsensor with interface whispering gallery modes.

Label-free sensors are highly desirable for biological analysis and early-stage disease diagnosis. Optical evanescent sensors have shown extraordinary ability in label-free detection, but their potentials have not been fully exploited because of the weak evanescent field tails at the sensing surfaces. Here, we report an ultrasensitive optofluidic biosensor with interface whispering gallery modes in a microbubble cavity. The interface modes feature both the peak of electromagnetic-field intensity at the sensing surface and high-Q factors even in a small-sized cavity, enabling a detection limit as low as 0.3 pg/cm2 The sample consumption can be pushed down to 10 pL due to the intrinsically integrated microfluidic channel. Furthermore, detection of single DNA with 8 kDa molecular weight is realized by the plasmonic-enhanced interface mode.

High-Entropy Strategy to Achieve Electronic Band Convergence for High-Performance Thermoelectrics.

Multiband convergence has attracted significant interest due to its positive effects on further improving thermoelectric performance. However, the current research mainly focuses on two- or three-band convergence in lead chalcogenides through doping and alloying. Therefore, exploring a new strategy to facilitate more-band convergence has instructive significance and practical value in thermoelectric research. Herein, we first propose a high-entropy strategy to achieve four-band convergence for optimizing thermoelectric performance. Taking high-entropy AgSbPbSnGeTe5 as an example, we found that the emergence of more-band convergence occurs as the configuration entropy increases; in particular, the four-band convergence occurs in high-entropy AgSbPbSnGeTe5. The overlap of multiatom orbitals in the high-entropy sample contributes to the convergence of four valence bands, promoting the improvement of electrical performance. Meanwhile, due to large lattice distortion and disordered atoms, the phonon mean free path is effectively compressed, resulting in low lattice thermal conductivity of high-entropy AgSbPbSnGeTe5. Consequently, AgSbPbSnGeTe5 achieved an intrinsically high ZT value of 1.22 at 673 K, providing a cornerstone for further optimizing thermoelectric performance. For example, by generally optimizing the carrier concentration, a peak ZT value of ∼1.75 at 723 K is achieved. These insights offer a comprehensive understanding of the band structure affected by unique structures of high-entropy materials and also shed useful light on innovation mechanisms and functionalities for future improvement of thermoelectric performance.

Interlayer Phonon Coupling from Heavy and Light Sublayers in a Natural Van der Waals Superlattice.

Layered compounds characterized by van der Waals gaps are often associated with relatively weak interlayer particle interactions. However, in specific scenarios, these seemingly feeble forces can exert an impact on interlayer interactions through subtle energy fluctuations, which can give rise to a diverse range of physical and chemical properties, particularly intriguing in the context of thermal transport. In this study, taking a natural superlattice composed of alternately stacked PbS and SnS2 sublayers as a model, we proposed that in a superlattice, there is strong hybridization between acoustic phonons of heavy sublayers and optical phonons of light sublayers. We identified newly generated vibration modes in the superlattice, such as interlayer shear and breathing, which exhibit lower sound velocity and contribute less to heat transport compared to their parent materials, which significantly alters the thermal behaviors of the superlattice compared to its bulk counterparts. Our findings on the behavior of interlayer phonons in superlattices not only can shed light on developing functional materials with enhanced thermal dissipation capabilities but also contribute to the broader field of condensed matter physics, offering insights into various fields, including thermoelectrics and phononic devices, and may pave the way for technological advancements in these areas.

Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets.

Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion-fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion-fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion-fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Sex differences in colorectal cancer: with a focus on sex hormone-gut microbiome axis.

Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of 'microgenderome' and 'sex hormone-gut microbiome axis.' Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone-gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment.

Dual-Plasmon Resonance Coupling Promoting Directional Photosynthesis of Nitrate from Air.

Photocatalysis, particularly plasmon-mediated photocatalysis, offers a green and sustainable approach for direct nitrogen oxidation into nitrate under ambient conditions. However, the unsatisfactory photocatalytic efficiency caused by the limited localized electromagnetic field enhancement and short hot carrier lifetime of traditional plasmonic catalysts is a stumbling block to the large-scale application of plasmon photocatalytic technology. Herein, we design and demonstrate the dual-plasmonic heterojunction (Bi/Csx WO3 ) achieves efficient and selective photocatalytic N2 oxidation. The yield of NO3 - over Bi/Csx WO3 (694.32 µg g-1 h-1 ) are 2.4 times that over Csx WO3 (292.12 µg g-1 h-1 ) under full-spectrum irradiation. The surface dual-plasmon resonance coupling effect generates a surge of localized electromagnetic field intensity to boost the formation efficiency and delay the self-thermalization of energetic hot carriers. Ultimately, electrons participate in the formation of ⋅O2 - , while holes involve in the generation of ⋅OH and the activation of N2 . The synergistic effect of multiple reactive oxygen species drives the direct photosynthesis of NO3 - , which achieves the overall-utilization of photoexcited electrons and holes in photocatalytic reaction. The concept that the dual-plasmon resonance coupling effect facilitates the directional overall-utilization of photoexcited carriers will pave a new way for the rational design of efficient photocatalytic systems.

Construction of Asymmetrical Dual Jahn-Teller Sites for Photocatalytic CO2 Reduction.

Photocatalytic CO2 reduction (PCR) expresses great attraction to convert useless greenhouse gas into valuable chemical feedstock. However, the weak interactions between catalytic sites and PCR intermediates constrains the PCR activity and selectivity. Herein, we proposed a new strategy to match the intermediates due to the maximum orbital overlap of catalytic sites and C1 intermediates by establishing dual Jahn-Teller (J-T) sites, in which, the strongly asymmetric J-T sites can break the nonpolar CO2 molecules and self-adapt the different structure of C1 intermediates. Taking cobalt carbonate hydroxide as an example, the weakly symmetric dual cobalt (Co2 ) dual J-T sites, weakly asymmetric Fe&Co sites and strongly asymmetric Cu&Co sites were assembled. After illumination, the interaction between dual J-T sites and the CO2 molecules enhances J-T distortion, which further modulates the PCR activity and selectivity. As a result, the Cu&Co sites exhibited CO yield of 8137.9 µmol g-1 , about 2.3-fold and 4.2-fold higher than that of the Fe&Co and Co2 sites within 5-hour photoreaction, respectively. In addition, the selectivity achieved as high as 92.62 % than Fe&Co (88.67 %) and Co2 sites (55.33 %). This work provides a novel design concept for the construction of dual J-T sites to regulate the catalytic activity and selectivity.

Maldistribution of Chemical Bond Strength Inducing Exceptional Anisotropy of Thermal Conductivity in Non-Layered Materials.

Currently, the efforts to find materials with high κ anisotropy ratios mainly focus on layered materials, however, the limited quantity and lower workability comparing to non-layered ones boost the exploration of non-layered materials with high κ anisotropy ratios. Here, taking PbSnS3 , a typical non-layered orthorhombic compound, as an example, we propose that maldistribution of chemical bond strength can lead to large anisotropy of κ in non-layered materials. Our result reveals that the maldistribution of Pb-S bonds lead to obvious collective vibrations of dioctahedron chain units, resulting in an anisotropy ratio up to 7.1 at 200 K and 5.5 at 300 K, respectively, which is one of the highest ever reported in non-layered materials and even surpasses many classical layered materials such as Bi2 Te3 and SnSe. Our findings can not only broaden the horizon for exploring high anisotropic κ materials but also provide new opportunities for the application of thermal management.

Bulk Superlattice Analogues for Energy Conversion.

Energy storage and conversion in a clean, efficient, and safe way is the core appeal of a modern sustainable society, which is built on the development of multifunctional materials. Superlattice structures can integrate the advantage of their sublayers while new phenomena may arise from the interface, which play key roles in modern semiconductor technology; however, additional concerns such as stability and yield challenge their large-scale applications in industrial products. In this Perspective we focus our interest on a distinctive category of easily available multilayered inorganic materials that have well-defined subunit structures and can be regarded as bulk superlattice analogues. We illustrate several specific combining forms of subunits in bulk superlattice analogues, including soft/rigid sublayers, electron/phonon transport sublayers, quasi-two-dimensional layers, and intercalated metal layers. We hope to provide insights into material design and broaden the application scope in the field of energy conversion by integrating the versatility of subunits into these bulk superlattice analogues.

In Situ Raman Monitoring of Potential-Dependent Adlayer Structures on the Au(111)/Ionic Liquid Interface.

Probing the adlayer structures on an electrode/electrolyte interface is one of the most important tasks in modern electrochemistry for clarifying the electrochemical processes. Herein, we have combined cyclic voltammetry and electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy techniques to explore the potential-dependent adlayer structures on Au(111) in a room-temperature ionic liquid of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF6) without or with pyridine (Py). It is clearly found that the BMI+ cations strongly adsorb on the negatively charged surface with a flat-lying orientation, leaving a little space for Py adsorption. Upon increasing the potentials of the electrode, the variations of Raman band intensities and frequencies reveal that the interaction between the BMI+ cations and the Au surface becomes weak; meanwhile, the Py adsorption becomes strong, and its geometry turns from flat, tilted to vertical. Finally, BMI+ cations desorb and leave plenty of surface sites for Py adsorption in bulk solution, and a N-bonded compact Py adlayer is formed on the very positively charged surface. This causes obvious anodic peaks in cyclic voltammograms, and the peak currents increase with the square root of the scanning rate. The present work provides a fair molecular-level understanding of electrochemical interfaces and molecular adsorption of Py in ionic liquids.

Electrochemically activated carbon-halogen bond cleavage and C-C coupling monitored by in situ shell-isolated nanoparticle-enhanced Raman spectroscopy.

The electroreductive cleavage of carbon-halogen bonds has attracted increasing attention in both electrosynthesis and pollution remediation. Herein, by employing the in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique, we have successfully investigated the electroreductive dehalogenation process of aryl halides with the thiol group on a smooth Au electrode in aqueous solution at different pH values. The obtained potential-dependent Raman spectra directly reveal a mixture of the reduction products 4,4'-biphenyldithiol (BPDT) and thiophenol (TP). The conversion ratios of the C-Cl and C-Br bonds at pH = 7 are 37% and 55%, respectively. Furthermore, quantitative analysis of the intensity variations of ν(C-Cl), ν(C-Br) and aromatic ν(CC) stretching modes suggests electroreductive dehalogenation via both direct electron transfer reduction and electrocatalytic hydrodehalogenation. Molecular evidence for the C-C cross coupling process through TP reaction with benzene free radical intermediates is found at negative potentials, which leads to the increasing selectivity of biphenyl products.

Dual Nanoislands on Ni/C Hybrid Nanosheet Activate Superior Hydrazine Oxidation-Assisted High-Efficiency H2 Production.

Clean hydrogen evolution through electrochemical water splitting underpins various innovative approaches to the pursuit of sustainable energy conversion technologies, but it is blocked by the sluggish anodic oxygen evolution reaction (OER). The hydrazine oxidation reaction (HzOR) has been considered as one of the most promising substitute for OER to improve the efficiency of hydrogen evolution reaction (HER). Herein, we construct novel dual nanoislands on Ni/C hybrid nanosheet array: one kind of island represents the part of bare Ni particle surface, while the other stands for the part of core-shell Ni@C structure (denoted as Ni-C HNSA), in which exposed Ni atoms and Ni-decorated carbon shell perform as active sites for HzOR and HER respectively. As a result, when the current density reaches 10 mA cm-2 , the working potentials are merely -37 mV for HER and -20 mV for HzOR. A two-electrode electrolyzer exhibits superb activity that only requires an ultrasmall cell voltage of 0.14 V to achieve 50 mA cm-2 .

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice.

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.

Artificial Heterointerfaces Achieve Delicate Reaction Kinetics towards Hydrogen Evolution and Hydrazine Oxidation Catalysis.

Electrochemical water splitting for H2 production is limited by the sluggish anode oxygen evolution reaction (OER), thus using hydrazine oxidation reaction (HzOR) to replace OER has received great attention. Here we report the hierarchical porous nanosheet arrays with abundant Ni3 N-Co3 N heterointerfaces on Ni foam with superior hydrogen evolution reaction (HER) and HzOR activity, realizing working potentials of -43 and -88 mV for 10 mA cm-2 , respectively, and achieving an industry-level 1000 mA cm-2 at 200 mV for HzOR. The two-electrode overall hydrazine splitting (OHzS) electrolyzer requires the cell voltages of 0.071 and 0.76 V for 10 and 400 mA cm-2 , respectively. The H2 production powered by a direct hydrazine fuel cell (DHzFC) and a commercial solar cell are investigated to inspire future practical applications. DFT calculations decipher that heterointerfaces simultaneously optimize the hydrogen adsorption free energy (ΔGH* ) and promote the hydrazine dehydrogenation kinetics. This work provides a rationale for advanced bifunctional electrocatalysts, and propels the practical energy-saving H2 generation techniques.

Parasitic Ferromagnetism in Few-Layered Transition-Metal Chalcogenophosphate.

Since the rise of two-dimensional (2D) semiconductors, it seems that electronic devices will soon be upgraded with spintronics, in which the manipulation of spin degree of freedom endows it obvious advantages over conventional charge-based electronics. However, as the most crucial prerequisite for the above-mentioned expectation, 2D semiconductors with adjustable magnetic interaction are still rare, which has greatly hampered the promotion of spintronics. Recently, transition metal phosphates have attracted tremendous interest due to their intrinsic antiferromagnetism and potential applications in spintronics. In the work described herein, parasitic ferromagnetism is achieved for the first time by exfoliating an antiferromagnetic chalcogenophosphate to a few layers. Taking the transition metal chalcogenophosphate Mn2P2S6 as an example, the antiferromagnetic transition at the Néel temperature is completely suppressed, and the magnetic behaviors of the as-obtained few-layered Mn2P2S6 are dominated by parasitic ferromagnetism. We experimentally verify an electron redistribution by which part of the Mn 3d electrons migrate and redistribute on P atoms in few-layered Mn2P2S6 due to the introduced Mn vacancies. The results demonstrated here broaden the tunability of the material's magnetic properties and open up a new strategy to rationally design the magnetic behaviors of 2D semiconductors, which could accelerate the applications of spintronics.

Hf(OTf)4 as a Highly Potent Catalyst for the Synthesis of Mannich Bases under Solvent-Free Conditions.

Hf(OTf)4 was identified as a highly potent catalyst (0.1-0.5 mol%) for three-component Mannich reaction under solvent-free conditions. Hf(OTf)4-catalyzed Mannich reaction exhibited excellent regioselectivity and diastereoselectivity when alkyl ketones were employed as substrates. 1H NMR tracing of the H/D exchange reaction of ketones in MeOH-d4 indicated that Hf(OTf)4 could significantly promote the keto-enol tautomerization, thereby contributing to the acceleration of reaction rate.

Progresses in the plant 3D chromatin architecture.

Chromatin architecture involves the patterns of chromatin coiling and packing as well as the mutual relative allocations of different chromatins. Besides the canonical microscopic observations, the chromatin architectural capture techniques, including the Hi-C and ChIA-PET, have been widely applied in characterization of chromatin architecture in various plant and animal model species, in which chromatin architectural features, such as the chromosome territory, compartment A/B, topological associated domains (TADs) and chromatin loops, were defined. As for the studies in plant species, replying on the two techniques above (with differences in experimental techniques and data structures), scientists have compared the variation of specific chromatin architecture features across species and/or in different cell types of the same plant species, besides detailed analyses in each individual model. Here, we mainly review the recent progresses in studies of plant chromatin architectures, in which their composition, establishing mechanism and effective factors were described and discussed. We also propose the main technical bottlenecks, describe the breaking-through progresses, and anticipate future research directions, which may offer more theoretical references for related researches in the field.

Natural Soft/Rigid Superlattices as Anodes for High-Performance Lithium-Ion Batteries.

Volume expansion and poor conductivity are two major obstacles that hinder the pursuit of the lithium-ion batteries with long cycling life and high power density. Herein, we highlight a misfit compound PbNbS3 with a soft/rigid superlattice structure, confirmed by scanning tunneling microscopy and electrochemical characterization, as a promising anode material for high performance lithium-ion batteries with optimized capacity, stability, and conductivity. The soft PbS sublayers primarily react with lithium, endowing capacity and preventing decomposition of the superlattice structure, while the rigid NbS2 sublayers support the skeleton and enhance the migration of electrons and lithium ions, as a result leading to a specific capacity of 710 mAh g-1 at 100 mA g-1 , which is 1.6 times of NbS2 and 3.9 times of PbS. Our finding reveals the competitive strategy of soft/rigid structure in lithium-ion batteries and broadens the horizons of single-phase anode material design.