Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells.

Self-renewal of spermatogonial stem cells is vital to lifelong production of male gametes and thus fertility. However, the underlying mechanisms remain enigmatic. Here, we show that DOT1L, the sole H3K79 methyltransferase, is required for spermatogonial stem cell self-renewal. Mice lacking DOT1L fail to maintain spermatogonial stem cells, characterized by a sequential loss of germ cells from spermatogonia to spermatids and ultimately a Sertoli cell only syndrome. Inhibition of DOT1L reduces the stem cell activity after transplantation. DOT1L promotes expression of the fate-determining HoxC transcription factors in spermatogonial stem cells. Furthermore, H3K79me2 accumulates at HoxC9 and HoxC10 genes. Our findings identify an essential function for DOT1L in adult stem cells and provide an epigenetic paradigm for regulation of spermatogonial stem cells.

The DOT1L-MLLT10 complex regulates male fertility and promotes histone removal during spermiogenesis.

Histone modifications regulate chromatin remodeling and gene expression in development and diseases. DOT1L, the sole histone H3K79 methyltransferase, is essential for embryonic development. Here, we report that DOT1L regulates male fertility in mouse. DOT1L associates with MLLT10 in testis. DOT1L and MLLT10 localize to the sex chromatin in meiotic and post-meiotic germ cells in an inter-dependent manner. Loss of either DOT1L or MLLT10 leads to reduced testis weight, decreased sperm count and male subfertility. H3K79me2 is abundant in elongating spermatids, which undergo the dramatic histone-to-protamine transition. Both DOT1L and MLLT10 are essential for H3K79me2 modification in germ cells. Strikingly, histones are substantially retained in epididymal sperm from either DOT1L- or MLLT10-deficient mice. These results demonstrate that H3K79 methylation promotes histone replacement during spermiogenesis.

Design, in silico evaluation, and in vitro verification of new bivalent Smac mimetics with pro-apoptotic activity.

Bivalent Smac mimetics have been shown to possess binding affinity and pro-apoptotic activity similar to or more potent than that of native Smac, a protein dimer able to neutralize the anti-apoptotic activity of an inhibitor of caspase enzymes, XIAP, which endows cancer cells with resistance to anticancer drugs. We design five new bivalent Smac mimetics, which are formed by various linkers tethering two diazabicyclic cores being the IAP binding motifs. We built in silico models of the five mimetics by the TwistDock workflow and evaluated their conformational tendency, which suggests that compound 3, whose linker is n-hexylene, possess the highest binding potency among the five. After synthesis of these compounds, their ability in tumour cell growth inhibition and apoptosis induction displayed in experiments with SK-OV-3 and MDA-MB-231 cancer cell lines confirms our prediction. Among the five mimetics, compound 3 displays promising pro-apoptotic activity and deserves further optimization.

Hybrid Interface Chemistry Enabling Mixed Conducting via Ultrafast Microwave Polarization Toward Dendrite-Free Zn Anodes.

Zn metal anodes in aqueous electrolytes suffer from interface issues including uncontrolled dendrite growth and undesired side reactions, resulting in their limited application in terms of short circuits and cell failure. Herein, a hybrid interface chemistry strategy is developed through ultrafast microwave polarization at the skin region of bare Zn. Owing to efficient Joule heating directed by abundant local hot spots at electron valleys, the rapid establishment of a dense interfacial layer can be realized within a minute. Stabilized Zn with suppressed side reactions or surface corrosion is therefore achieved due to the interfacial protection. Importantly, hybrid zincophilic sites involving laterally/vertically interconnected Cu-Zn intermetallic compound and Zn2+-conductive oxide species ensure mixed charge conducting (denoted as CuHL@Zn), featuring uniformly distributed electric field and boosted Zn2+ diffusion kinetics. As a consequence, CuHL@Zn in symmetric cells affords lifespans of 2800 and 3200 h with ultra-low polarization voltages (≈19 and 56 mV) at a plating capacity of 1.0 mAh cm-2 for 1 and 5 mA cm-2, respectively. The CuHL@Zn||MnO2 full cell further exhibits cycling stability with a capacity retention of over 80% for 500 cycles at 2 A g-1.

A novel strategy to construct hydrogels with anti-swelling and water-retention abilities by covalent surface modification.

Hydrogels have been widely used in various fields due to their diverse properties and flexible preparation methods. However, limited by the open network structure, hydrogels inevitably lose water in air or absorb water in aqueous solution, resulting in the loss of intrinsic functions, which severely hinders their practical applications. To address this issue, a general strategy was developed by subsequently modifying the surface of hydrogels with branched polyethyleneimine (PEI) and (3-(methacryloxy)propyl)trimethoxysilane (MPS) to covalently construct a dense cross-linked siloxane layer on the hydrogel surface. As a proof of concept, poly(2-(dimethylamino)ethyl methacrylate)/sodium alginate (PDMAEMA/SA) hydrogels were chosen as the model hydrogels to verify the feasibility of this strategy. The hydrogels adsorbed PEI to form amino-rich surfaces through hydrogen bonding, followed by covalently grafting MPS through rapid and catalyst-free mutual chemical reactions between acrylates and amine groups, as well as the hydrolysis of MPS. After modification, robust hydrophobic surfaces were successfully fabricated on the hydrophilic hydrogels. The modified hydrogels exhibited extraordinary anti-swelling and water-retention abilities. As the most typical intrinsic properties of hydrogels, the conductivity and sensing performance were well preserved. The strategy reported here provides a new insight into the construction of hydrogels with anti-swelling and water-retention abilities.

SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination.

Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.

Tendon-Inspired Anisotropic Hydrogels with Excellent Mechanical Properties for Strain Sensors.

Anisotropic conductive hydrogels mimicking the natural tissues with high mechanical properties and intelligent sensing have played an important role in the field of flexible electronic devices. Herein, tensile remodeling, drying, and subsequent ion cross-linking methods were used to construct anisotropic hydrogels, which were inspired by the orientation and functionality of tendons. Due to the anisotropic arrangement of the polymer network, the mechanical performance and electrical conductivity were greatly improved in specific directions. The tensile stress and elastic modulus of the hydrogel along the network orientation were 29.82 and 28.53 MPa, which were higher than those along the vertical orientation, 9.63 and 11.7 MPa, respectively. Moreover, the hydrogels exhibited structure-dependent anisotropic sensing. The gauge factors (GFs) parallel to the prestretching direction were greater than the GF along the vertical direction. Thus, the tendon-inspired conductive hydrogels with anisotropy could be used as flexible sensors for joint motion detection and voice recognition. The anisotropic hydrogel-based sensors are highly expected to promote the great development of emerging soft electronics and medical detection.

Ultrafast Microwave Activating Polarized Electron for Scalable Porous Al toward High-Energy-Density Batteries.

Chemical etching of metals generally brings about undesirable surface damage accompanied by deteriorated performance. However, new possibilities in view of structured interfaces and functional surfaces can be explored by wisely incorporating corrosion chemistry. Here, an ultrafast route to scalable Al foils with desired porous structures originating from Fe(III)-induced oxidation etching was presented. Coupling with efficient electron polarization involving microwave interaction, straightforward surface engineering is well established on various commercial Al foils within minutes, which can be successfully extended to bulk Al alloys. As a proof-of-concept demonstration, the well-defined porous Al foils featuring regulated surface energy, demonstrate great potential as current collectors in promoting cycling stability, for example, 85.2% reversible capacity sustained after 550 cycles (comparable to commercial Al/C foils), and energy density, that is, approximately 3 times of that by using pristine Al foils for LiFePO4-Li half cells.

Rational Design of a Flexible CNTs@PDMS Film Patterned by Bio-Inspired Templates as a Strain Sensor and Supercapacitor.

Flexible devices integrated with sensing and energy storage functions are highly desirable due to their potential application in wearable electronics and human motion detection. Here, a flexible film is designed in a facile and low-cost leaf templating process, comprising wrinkled carbon nanotubes (CNTs) as the conductive layer and patterned polydimethylsiloxane (PDMS) with bio-inspired microstructure as a soft substrate. Assembled from wrinkled CNTs on patterned PDMS film, a strain sensor is realized to possess sensitive resistance response against various deformations, producing a resistance response of 0.34%, 0.14%, and 9.1% under bending, pressing, and 20% strain, respectively. Besides, the strain sensor can reach a resistance response of 3.01 when stretched to 44%. Furthermore, through the electro-deposition of polyaniline, the CNTs film is developed into a supercapacitor, which exhibits a specific capacitance of 176 F g-1 at 1 A g-1 and a capacitance retention of 88% after 10 000 cycles. In addition, the fabricated supercapacitor shows super flexibility, delivering a capacitance retention of 98% after 180° bending for 100 cycles, 95% after 45° twisting for 100 cycles, and 98% after 100% stretching for 400 cycles. The superior capacitance stability demonstrates that the design of wrinkled CNTs-based electrodes fixed by microstructures is beneficial to the excellent electrochemical performance.

Recent Advances in Metal-Organic Frameworks for Photo-/Electrocatalytic CO2 Reduction.

Considerable attention has been paid to the utilization of CO2 , an abundant carbon source in nature. In this regard, porous catalysts have been eagerly explored with excellent performance for photo-/electrocatalytic reduction of CO2 to high valued products. Metal-organic frameworks (MOFs), featuring large surface area, high porosity, tunable composition and unique structural characteristics, have been widely exploited in catalytic CO2 reduction. This Minireview first reports the current progress of MOFs in CO2 reduction. Then, a specific interest is focused on MOFs in photo-/electrocatalytic reduction of CO2 by modifying their metal centers, organic linkers, and pores. Finally, the future directions of study are also highlighted to satisfy the requirement of practical applications.

Coaxial-cable hierarchical tubular MnO2@Fe3O4@C heterostructures as advanced anodes for lithium-ion batteries.

Nanostructured manganese oxides have been regarded as promising anodes for lithium-ion batteries (LIBs) due to their high specific capacity, environmental friendliness and low cost. However, as conversion-type electrodes, their scalable utilization is hindered by intrinsically low reaction kinetics, large volume variation and high polarization. Herein, a coaxial-cable tubular heterostructure composed of a hollow carbon skeleton, Fe3O4 nanoparticles and ultrathin MnO2 nanosheets from inside out, donated as MnO2@Fe3O4@C, is synthesized via a facile two-step hydrothermal process. The unique design integrates conductive carbon and nanostructured MnO2 and Fe3O4 into a one-dimensional (1D) hierarchically open architecture, which provides abundant electrode-electrolyte contact areas, favorable heterointerfaces and ultrafast electron/ion pathways. Benefiting from these features, the MnO2@Fe3O4@C anode exhibits a high reversible capacity of 946 mAh g-1 at 200 mA g-1 after 160 cycles, and excellent cyclability with a specific capacity of 845 mAh g-1 at 500 mA g-1 after 600 cycles. This work might provide an insightful guideline for the design of novel electrode materials.

Organic Molecule-Driven Polymeric Actuators.

Inspired by the motions of plant tissues in response to external stimuli, significant attention has been devoted to the development of actuating polymeric materials. In particular, polymeric actuators driven by organic molecules have been designed due to their combined superiorities of tunable functional monomers, designable chemical structures, and variable structural anisotropy. Here, the recent progress is summarized in terms of material synthesis, structure design, polymer-solvent interaction, and actuating performance. In addition, various possibilities for practical applications, including the ability to sense chemical vapors and solvent isomers, and future directions to satisfy the requirement of sensing and smart systems are also highlighted.

Topochemical Synthesis of 2D Carbon Hybrids through Self-Boosting Catalytic Carbonization of a Metal-Polymer Framework.

Two-dimensional (2D) carbon hybrids have promise in various areas such as energy storage and catalysis. Simple methods for controllable fabrication of 2D graphitic carbon hybrids in a scalable manner remains challenging. Now, a microwave-assisted strategy for mass production of 2D carbon hybrids based on self-boosting catalytic carbonization of a metal-agarose framework is demonstrated. Hybrids including hollow Fe3 C nanoparticles, Ni/Co nanoparticles, and hollow FeOx nanoparticles uniformly embedded in 2D graphitic carbon nanosheets (GCNs) are obtained, demonstrating the generality of the approach. Metal-polymer coordination and microwave-enabled fast catalytic decomposition of precursors play vital roles in facilitating the formation of the nanosheet structure. The resulting FeOx -GCNs hybrid exhibits superior lithium-storage performance (1118 mAh g-1 at 500 mA g-1 and 818 mAh g-1 at 2000 mA g-1 after 1200 cycles).

Winding aligned carbon nanotube composite yarns into coaxial fiber full batteries with high performances.

Inspired by the fantastic and fast-growing wearable electronics such as Google Glass and Apple iWatch, matchable lightweight and weaveable energy storage systems are urgently demanded while remaining as a bottleneck in the whole technology. Fiber-shaped energy storage devices that can be woven into electronic textiles may represent a general and effective strategy to overcome the above difficulty. Here a coaxial fiber lithium-ion battery has been achieved by sequentially winding aligned carbon nanotube composite yarn cathode and anode onto a cotton fiber. Novel yarn structures are designed to enable a high performance with a linear energy density of 0.75 mWh cm(-1). A wearable energy storage textile is also produced with an areal energy density of 4.5 mWh cm(-2).

TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis.

Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. Mouse TRIP13 and its ortholog Pch2 are instrumental in remodeling HORMA domain proteins. HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed homologs. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. Trip13-null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These major phenotypes are consistent with reported phenotypes of Trip13 hypomorph alleles. Trip13 heterozygous mice exhibit meiotic defects that are less severe than the Trip13-null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. Terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon synapsis in diverse organisms.

Novel basic protein, PfN23, functions as key macromolecule during nacre formation.

The fine microstructure of nacre (mother of pearl) illustrates the beauty of nature. Proteins found in nacre were believed to be "natural hands" that control nacre formation. In the classical view of nacre formation, nucleation of the main minerals, calcium carbonate, is induced on and by the acidic proteins in nacre. However, the basic proteins were not expected to be components of nacre. Here, we reported that a novel basic protein, PfN23, was a key accelerator in the control over crystal growth in nacre. The expression profile, in situ immunostaining, and in vitro immunodetection assays showed that PfN23 was localized within calcium carbonate crystals in the nacre. Knocking down the expression of PfN23 in adults via double-stranded RNA injection led to a disordered nacre surface in adults. Blocking the translation of PfN23 in embryos using morpholino oligomers led to the arrest of larval development. The in vitro crystallization assay showed that PfN23 increases the rate of calcium carbonate deposition and induced the formation of aragonite crystals with characteristics close to nacre. In addition, we constructed the peptides and truncations of different regions of this protein and found that the positively charged C-terminal region was a key region for the function of PfN23 Taken together, the basic protein PfN23 may be a key accelerator in the control of crystal growth in nacre. This provides a valuable balance to the classic view that acidic proteins control calcium carbonate deposition in nacre.

[Characteristics of Ozone Pollution and High-impact Meteorological Factors in Urban Cities: A Case of Suzhou].

The problem of urban ozone (O3) pollution has become prominent in recent years. However, the meteorological factors associated with O3 pollution remain unclear. Analyzing the characteristics of O3 pollution in Suzhou, as a typical urban city, and exploring the high-impact meteorological factors with O3 pollution are crucial to the prevention and control of air pollution in this region. This study used correlation analysis and machine learning methods to analyze the variation in O3 concentration and the relationship between meteorological driving factors in Suzhou based on the O3 concentration data provided by Suzhou Environmental Monitoring Center and the contemporaneous meteorological observation data in Suzhou from April to September in 2015 to 2020. The results showed that: ① O3 pollution exceeding the standard rate was more than 20% in ozone seasons during the past six years; further, pollution days of O3 and the number of pollution days of O3 as the primary pollutant increased yearly. Evidently, the problem of O3 pollution has become increasingly prominent. ② The diurnal variations in O3 were unimodal with the valley point at 07:00 and the highest peak between 15:00 and 16:00. Similar trends were found in diurnal variations of both air temperature and solar radiation, but the daily highest peak came earlier than that of O3. The results also showed an apparent weekend effect of O3 concentration in 2017 and 2019 and a significant correlation between O3 concentration and solar irradiance during the week. In addition, the monthly variation in O3 concentration and pollution exceeding the standard rate was bimodal. ③The occurrence of ozone pollution was affected by various meteorological conditions. The maximum number of days appeared when daily sunshine hours lasted longer than 7 hours, with a daily maximum air temperature around 30℃, solar irradiance ranging from 350 to 440 kW·m-2, and relative humidity ranging from 50% to 75%, at which time the intensity of pollution was the strongest. When the wind speed of easterly wind was less than 1.5 m·s-1, or the wind speed of southwest wind was less than 3.5 m·s-1, moderate ozone pollution occurred. ④ An optimal prediction model of O3 concentration was established based on machine learning, which had good predictive ability for O3 concentration in April, May, July, and September but did not perform well when O3 concentration exceeded 200 µg·m-3. Meanwhile, it was found that solar radiation had the most obvious effect on O3 concentration, followed by relative humidity, whereas the temperature and wind were less important than the former two factors.

Piezoresistive Pressure Sensor Based on a Conductive 3D Sponge Network for Motion Sensing and Human-Machine Interface.

Flexible sensors have attracted increasing attention owing to their important applications in human activity monitoring, medical diagnosis, and human-machine interaction. However, the rational design of low-cost sensors with desirable properties (e.g., high sensitivity and excellent stability) and extended applications is still a great challenge. Herein, a simple and cost-effective strategy is reported by immersing polyurethane (PU) sponge in graphene oxide solution followed by in situ chemical reduction to construct a reduced graphene oxide (RGO)-wrapped PU sponge sensor. Ascribed to the excellent compressive resilience of PU sponge and an electrically conductive RGO layer, the constructed flexible sensor exhibits satisfactory sensing performance with high sensitivity (17.65 kPa-1) in a low-load range (0-3.2 kPa), a wide compression strain range (0-80%), and reliable stability (8000 cycles). In addition, these sensors can be successfully applied to monitor human movements and identify the weight of objects. Through the use of a sensor array integrated with a signal acquisition circuit, the reasonably designed sensors can realize tactile feedback via mapping real-time spatial distribution of pressure in complicated tasks and show potential applications in flexible electronic pianos, electronic skin, and remote real-time control of home electronics.

TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis.

Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. The AAA+ ATPase TRIP13 and its orthologue Pch2 are instrumental in remodeling HORMA domain proteins. Meiosis-specific HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed chromosome homologues. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. Trip13-null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These findings confirm the previously reported phenotypes of the Trip13 hypomorph alleles. Trip13 heterozygous (Trip13+/-) mice also exhibit meiotic defects that are less severe than the Trip13-null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. The N- or C-terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres in knockin mice. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon chromosome synapsis in diverse organisms.

[Effects of moxibustion at Yongquan (KI 1) on cognition function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency].

OBJECTIVE: To observe the effects of moxibustion at Yongquan（KI 1） on the cognitive function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency. METHODS: Eighty-four patients with post-stroke cognitive impairment of kidney essence deficiency were randomly divided into an observation group（42 cases，1 case dropped off）and a control group（42 cases，1 case dropped off）.The control group was treated with medication，electroacupuncture，rehabilitation training and repetitive transcranial magnetic stimulation（rTMS）；on the basis of the treatment as the control group，moxibustion at bilateral Yongquan（KI 1）was adopted in the observation group.Both groups were treated once a day，5 days a week with 2-day interval，4 weeks were required. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, Fugl-Meyer assessment-lower extremity (FMA-LE) score, Berg balance scale (BBS) score, functional independence measure (FIM) score, modified fall efficacy scale (MFES) score and scale for the differentiation of syndromes of vascular dementia (SDSVD) score before and after treatment were observed in the two groups. RESULTS: After treatment，the MoCA, MMSE, FMA-LE, BBS, FIM and MFES scores were higher than those before treatment in both groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment，the SDSVD scores were lower than those before treatment in both groups (P< 0.05), and the SDSVD score in the observation group was lower than that in the control group (P< 0.05). CONCLUSION: Moxibustion at Yongquan（KI 1） can improve the cognitive function and motor and balance function of lower limbs in patients with post-stroke cognitive impairment of kidney essence deficiency，reduce the risk of fall and improve the quality of life.