Search

Generating highly organized skeletal muscle tissues that mimics the cellular alignment, maturation, and contraction of native skeletal muscle remains a challenge in disease modeling and regenerative therapies. Existing methodologies are constrained by complexity in fabrication and difficulty in achieving aligned 3D myofibers. Here, a functional skeletal muscle organoid‐on‐a‐chip (SMO) is engineered by establishing mechanical boundary constraints at either end of the cell‐laden extracellular matrix hydrogel within polydimethylsiloxane microstructures to promote the formation of an anisotropic biophysical microenvironment in tissues. The linearly aligned tissue, featuring multinucleated myofibers with distinct cross‐striations, exhibited a positive force‐frequency relationship and stable calcium transients under electrical stimulation. SMOs applicability is demonstrated by systematically evaluating muscle response to varying degrees of intermittent hypoxia. Murine‐ or human‐derived SMOs revealed that, with increasing hypoxia severity, muscles transitioned from a compensatory phase‐characterized by enhanced contractile function, vacuolation and hypertrophic‐like changes in myofibers, fiber type switching, and metabolic shift, to a decompensatory stage, paralleling in vivo muscle responses and highlighting interspecies differences. Human‐derived SMOs are also utilized to assess self‐repair capabilities and pharmaceuticals protective effects on damaged muscle. Together, the platform, with its simplicity of operation and reliable phenotypic readouts, demonstrates significant potential for future disease modeling and regenerative therapies. [ABSTRACT FROM AUTHOR]

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro‐inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro‐inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3‐hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti‐inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage. [ABSTRACT FROM AUTHOR]

Summary: This study investigates the seismic impact of concrete floors on reduced beam section beam‐to‐column joints through four quasi‐static cyclic tests. We examine mechanical properties, failure modes, and processes against specific criteria. Additionally, we analyze hysteretic response, energy dissipation, stiffness, capacity, and stress–strain mechanisms. Moreover, the ABAQUS platform was used to reproduce the specimen nonlinear finite element model to compare and analyze the test results. The results showed that the specimens exhibit excellent energy dissipation capacity and ductility (with a coefficient of 5.00); the column‐bar connection characteristics affect the maximum capacity and plastic hinge behavior in the reduced beam area. The reduced section of beam's upper flange could not improve the overall seismic performance of the joint. The observed failure sequence is as follows: concrete floor cracking, beam flange yielding, reinforcement fracture, lower flange yielding in the reduced beam area, and overall joint failure. This sequence confirms that the joint fulfills the design criteria of a "strong column‐weak beam" by achieving the target of plastic hinge outward movement. [ABSTRACT FROM AUTHOR]

Under physical conditions such as TC = 68 °C, Vanadium dioxide (VO2) undergoes a reversible transformation from a monoclinic phase to a tetragonal rutile phase. This transformation is accompanied by a series of changes in physical properties, including transmittance, conductivity, and refractive index, which make it an excellent functional material. Based on this, VO2 has been extensively researched and applied in the fields of electronics and optics, yielding remarkable results and making it a hot research material. This paper reviews the phase transition mechanisms and optical/electrical properties of VO2, as well as its phase transition hysteresis. From the application perspective, this paper summarizes the modulation content under various external excitations and the element doping effects. Finally, this paper summarizes the classic VO2‐based devices, and points out the development direction and potential of VO2 in optics and electronics. This review provides a systematic summary of VO2, which is useful for its practical applications. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a zoonotic parasite infecting humans and nearly all warm‐blooded animals. Successful parasitism in diverse hosts at various developmental stages requires the parasites to fine tune their metabolism according to environmental cues and the parasite's needs. By manipulating the β and γ subunits, we have previously shown that AMP‐activated protein kinase (AMPK) has critical roles in regulating the metabolic and developmental programmes. However, the biological functions of the α catalytic subunit have not been established. T. gondii encodes a canonical AMPKα, as well as a KIN kinase whose kinase domain has high sequence similarities to those of classic AMPKα proteins. Here, we found that TgKIN is dispensable for tachyzoite growth, whereas TgAMPKα is essential. Depletion of TgAMPKα expression resulted in decreased ATP levels and reduced metabolic flux in glycolysis and the tricarboxylic acid cycle, confirming that TgAMPK is involved in metabolic regulation and energy homeostasis in the parasite. Sequential truncations at the C‐terminus found an α‐helix that is key for the function of TgAMPKα. The amino acid sequences of this α‐helix are not conserved among various AMPKα proteins, likely because it is involved in interactions with TgAMPKβ, which only have limited sequence similarities to AMPKβ in other eukaryotes. The essential role of the less conserved C‐terminus of TgAMPKα provides opportunities for parasite specific drug designs targeting TgAMPKα. [ABSTRACT FROM AUTHOR]

Although colloidal perovskite nanocrystal (PNC) solution has exhibited near‐unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non‐radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light‐emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close‐packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect‐free high‐quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %. [ABSTRACT FROM AUTHOR]

In recent years, with the rapid development of military, optical communication, biological imaging, and other fields, practical engineering applications such as fiber‐optic gyroscope, wavelength division multiplexing, and optical coherence tomography have put forward higher requirements on light sources. Amplified spontaneous emission (ASE) light source has become an excellent candidate due to its advantages such as suitable bandwidth, low coherence, and high power. Although the ASE light source is developed to a certain extent, there is still great room for improvement in the choice of gain medium and device structure. In order to accelerate the development and practical engineering application of ASE optoelectronic devices, it is of great significance to grasp the basic characteristics of the gain materials and the design of the device structure. In this review, the principle of the ASE effect and its difference with the generation of lasing are analyzed. Then, the optical gain properties of various gain materials, together with different structural types of electrically pumped ASE devices and their practical engineering applications, are summarized. Finally, the new ASE light‐emitting devices integrated with high‐gain materials and low‐cost structures are prospected to provide more ideas for their development. [ABSTRACT FROM AUTHOR]

This study investigates the intermodel spread of changes in the Eurasian winter surface air temperature (SAT) based on Coupled Model Intercomparison Project 6 (CMIP6) and explains it from the perspective of circulation under shared socioeconomic pathway 2–4.5. Results show that the leading intermodel spread of Eurasian SAT change, derived from the intermodel empirical orthogonal function analysis (EOF), is characterized by a warming pattern of SAT change. This warming pattern is associated with the changes in the weakened Siberian High and Aleutian Low, the weakened subtropical jet, the poleward polar jet, and the tilting trough. The combination of these circulations has prevented the intrusion of the cold air to the south and therefore results in the warming SAT change pattern. Their relative contribution weights of the weakened Siberian High and Aleutian Low, the tilting East Asian trough, the weakened subtropical jet, and the poleward polar jet are 12.73%, 20.43%, 30.24%, 20.96%, and 15.64%, respectively. All these changes may be traced to the warm sea surface temperature (SST) changes in the western North Pacific and tropical Atlantic Ocean, via the meridional temperature gradient and wave trains, respectively. These warmings would be the potential metrics for reducing the intermodel uncertainties of the winter SAT projection at the end of the 21st century over the Eurasian continent. Plain Language Summary: There are still large intermodel uncertainties in the projection of the winter SAT over the Eurasian continent. In this study, the intermodel EOF is utilized to derive the intermodel spread in the winter SAT change at the end of the 21st century over the Eurasian continent. The leading mode is a warming pattern over Eurasia, which is closely related to the large‐scale circulations, including the changes in the weakened Siberian High and Aleutian Low, the tilt of the East Asian trough, the weakened western subtropical jet, and the northward shift of the eastern polar front jet. All these changes may be traced to the warming in the western North Pacific and the tropical Atlantic. Our findings provide a perspective to improve the projection of Eurasian winter SAT. Key Points: The leading intermodel spread in winter surface air temperature change at the end of the 21st century over the Eurasian continent is a warming pattern from the CMIP6 modelsThe large‐circulation changes in the sea‐level pressure, the tilting trough, and jets are highly associated with this intermodel spreadAll these changes might be traced to the warm SST changes in the western North Pacific and the tropical Atlantic [ABSTRACT FROM AUTHOR]

To investigate the cryoprotective effect of flammulina velutipes polysaccharide (FVP) on the quality characteristics in freeze‐thawed cultured large yellow croaker, 0.050%, 0.075%, and 0.100% FVP was used before freezing and the quality after thawing was compared with water soaking (WS) and commercial cryoprotectant (CC) treatment. Quality attributes were comprehensively determined instrumentally and organoleptically after thawing at 4°C. Results showed that FVP effectively reduces the quality deterioration of body color and water‐holding capacity, while no obvious effects were observed in texture and flavor. As for body color, both FVP and CC treatment could maintain the b* value to a large extent. Among them, 0.075% FVP shows the highest value in two sample points, with 55.2% and 21.0% increases seen in the values in WS. FVP‐dose‐dependent trends were found in water‐holding capacity, where a reduction of 28.26% and 14.38% in thawing loss and cooking loss was observed in the 0.100% FVP group. Low‐field nuclear magnetic resonance (LF‐NMR) also revealed that immobilized water and free water were more tightly retained in the muscle tissue with FVP addition. The results of the sensory evaluation are essentially in line with the above observations. These findings indicate that FVP has the potential to partially replace commercial cryoprotectants in aquatic products during frozen storage. [ABSTRACT FROM AUTHOR]

The model uncertainty, one of the major sources of projection uncertainty, is still a challenge in the climate simulation. In this study, we investigated the inter‐model spread of the simulated winter surface air temperature (SAT) over the Eurasian continent and the physical link to the upper‐level jet streams from the Coupled Model Inter‐comparison Project Phase 6 models. Extracted by the inter‐model empirical orthogonal function analysis, the leading inter‐model spread of SAT over the Eurasian continent is characterized by a cold pattern, particularly over high latitudes, which is closely associated with the out‐of‐phase variation in the intensity of the East Asian polar front jet (EAPJ) and East Asian subtropical jet (EASJ). The weakened‐EAPJ‐enhanced‐EASJ pattern is linked to the intensified Siberian high, the strengthened Aleutian low, and the deepened East Asian trough. All the variations would benefit the cold air invasion, resulting in the leading inter‐model spread of the SAT. The possible mechanism for the inter‐model uncertainty in the out‐of‐phase variation in the intensity of the two jets would be traced to the cooling over the Northwest Pacific oceans, which has reduced (enhanced) the meridional temperature gradient over high (low) latitudes and thereby contributed to the out of phase variation in the two jets. Our findings would help provide a potential metric for understanding the winter SAT change over the Eurasian continent. Plain Language Summary: The winter surface air temperature (SAT) over the Eurasian continent has profound economic and social impacts, however, there are large uncertainties in the climate model simulations. In this study, the inter‐model spread is utilized to derive the inter‐model uncertainty in the winter SAT over the Eurasian continent. The leading mode is a cold pattern over the Eurasian continent, which is closely related to the out‐of‐phase concurrent variation in the intensity of the upper‐level jet streams, resulting in the strengthened East Asian Winter monsoon. With an emphasis on the physical link between the East Asian jet streams and the winter SAT over the Eurasian continent, our findings provide a perspective of physical linkage to understand the traces of model uncertainty. Key Points: The leading inter‐model spread in winter surface air temperature over the Eurasian continent is a cold pattern from the CMIP6 modelsThe weakened‐East Asian polar front jet‐enhanced‐East Asian subtropical jet variation would result in this inter‐model spread due to the strengthened East Asian winter monsoonThe cooling spreads in the Northwest Pacific have physically linked this out‐of‐phase variation in the intensity of the two jets [ABSTRACT FROM AUTHOR]

Saltwater intrusion is a common feature in the Changjiang Estuary affected by river discharges and tidal flows. It leads to a two‐layer flow structure during the flood‐to‐ebb tidal transient period: the seaward tidal flow in the upper water column and onshore intruded salt flow in the lower column, even though the lower column water usually experiences an ebb flow eventually. Our recent measurements with a tripod deployed in a tidal channel of the North Branch in the East China Sea challenged this feature. We detected that the two‐layer flow structure disappeared in the ebb tide period during the neap cycle due to intense saltwater intrusion. A constant onshore flood‐like flow predominated the entire water column. The physical mechanism for the flow reversal was examined using the Finite Volume Community Ocean Model (FVCOM). The FVCOM was robust to capture the observed flow reversal in the tidal channel during the neap tidal cycle. The momentum balance analysis results suggest that the flow reversal occurred when the saltwater intrusion‐induced onshore baroclinic pressure gradient force and baroclinic tidal rectification overwhelmed the seaward barotropic pressure gradient force. A parameter‐driven criterion was derived theoretically to determine the potential occurrence of a stable ebb flow reversal in the tidal channel. Plain Language Summary: Many estuaries experience saltwater intrusion, bringing saltwater from offshore regions to nearshore and river channels. In the Changjiang Estuary, it could create a two‐layer flow structure during the flood‐to‐ebb transient period, a seaward fresher ebb tidal flow in the upper water column, and an onshore intruded salt flow in the lower water column. Could the increased saltwater intrusion destroy this two‐layer flow structure and form an onshore flow throughout the water column in the ebb‐tidal period during a neap tidal cycle? If it does, what is the critical driving mechanism? To answer these questions, we deployed a tripod system integrated with state‐of‐the‐art marine instruments in a tidal channel of North Branch in the Changjiang Estuary, an area where saltwater intrusion frequently occurs. The observational data captured a flow‐overtured feature, showing a stable flood‐like intruded flow throughout the entire water column in the ebb‐tidal period during a neap tidal cycle. We applied the Finite‐Volume Community Ocean Model to examine the physical driving mechanism for flow‐overturning. The results suggest that the flow‐overturning could occur when the along‐channel saltwater intrusion‐induced baroclinic pressure gradient force and stratified tidal rectification overwhelmed the along‐channel tide‐induced barotropic pressure gradient force. Key Points: The bottom tripod system identified an overturned tidal flow in the North Branch channelA numerical model revealed the baroclinic gradient force from saltwater intrusion dominated the overturnThe balance criteria were proposed to estimate competition between these two dynamics [ABSTRACT FROM AUTHOR]

The model uncertainty, one of the major sources of projection uncertainty, is still a challenge in the climate change projection. In this study, the model uncertainty in simulating the East Asian summer monsoon rainfall and its physical link to the upper‐level jet streams and the western North Pacific subtropical high (WNPSH) are investigated from the Coupled Model Inter‐comparison Project Phase 6 (CMIP6) models. The results show that extracted by the inter‐model Empirical Orthogonal Function method, the leading inter‐model mode of the rainfall is characterized as a meridional pattern. The positive mode (a continent‐wet‐ocean‐dry pattern) is closely associated with a northward shift of the oceanic branch of the East Asian subtropical jet and a northward movement of the WNPSH, while the negative mode (a continent‐dry‐ocean‐wet pattern) is highly correlated with an enhanced East Asian polar‐front jet combined with a weakened land branch of the East Asian subtropical jet as well as a weakened and eastward recess of the WNPSH. This systematic link among the atmospheric circulations and the leading inter‐model mode is maintained by the negative phase of the Victoria Mode in the North Pacific and warming over the Atlantic Ocean in the positive mode, and the cooling over the Indian Ocean, Atlantic Ocean and the warming over the central Pacific in the negative mode. Our findings suggest that the physical linkage between the atmospheric circulations and monsoon rainfall is useful to understand the model uncertainty, which would be helpful in providing potential indicators of the East Asia summer monsoon change. Plain Language Summary: Monsoon rainfall has profound economic and social impacts, however large uncertainties lie in the climate model simulations. In this study, the inter‐model spread is used to extract the model uncertainty for the East Asian summer monsoon rainfall. The leading inter‐model mode is a meridional dipole pattern, which is closely associated with the concurrent variations of jet streams and the intensity and meridional movement of the western North Pacific subtropical high (WNPSH), but with the asymmetric response. The associated jet stream and the WNPSH variations are sustained by the oceanic conditions over the Atlantic Ocean, Pacific Ocean, and Indian Ocean, and therefore results in the inter‐model spread of the monsoon rainfall. Our findings suggest a useful metric to understand the traces of model uncertainties, focused on the physical linkage between the atmospheric circulations and the monsoon rainfall. Key Points: The leading inter‐model spread in East Asian summer monsoon rainfall is a meridional pattern from the Coupled Model Inter‐comparison Project Phase 6 modelsThe associated jet streams and western North Pacific subtropical high (WNPSH) variations exhibit asymmetric responses to this inter‐model spreadThe uncertainties in the north Pacific, Atlantic, and Indian Ocean have physically linked the jet stream and WNPSH variations to this inter‐model spread [ABSTRACT FROM AUTHOR]

The rapid development of lasers since their launch has given a new lease to traditional optical technology and immensely boosted the development of natural science. Benefiting from the salient light absorption and light emission traits, perovskite lasers show incalculable prospects in applications of optical storage, optical interconnects, high‐quality displays, on‐chip photonic communications, etc. For perovskite lasers, device structure and working principle rather than just material property are also profound, especially for the realization and assessment of electrically pumped lasers, which is the prerequisite for the ultimate practical application of perovskite lasers. With this in mind, the key characteristic parameters of possible future electrically pumped lasers are discussed herein, and a systematic review of perovskite lasers is presented in a sequential order of development. To begin, the components of lasers are introduced in detail, with an emphasis on optical microcavities and diverse proposed working mechanisms, followed by introductions of representative advances in pulsed optically pumped perovskite lasers with various lasing modes, as well as state‐of‐the‐art developments in lasing phenomenon under continuous‐wave optical pumping. Finally, the challenges and fruitful progress toward electrically pumped perovskite lasers are discussed emphatically. It is hoped that this review will promote the realization of perovskite electrically pumped lasers and commercialization of perovskite lasers. [ABSTRACT FROM AUTHOR]

Developing flexible polyurethane foam (FPUF) with good anti‐ignition and self‐extinguishing performance is the fundamental way to prevent fire hazards in application. A binary composite system containing ammonium hypophosphite (NHP) and expandable graphite (EG) was applied to prepare flame‐retardant FPUF. The co‐action of NHP and EG exhibited high‐efficiency synergistic effect in improving the anti‐ignition, self‐extinguishing, and carbonization performance of FPUF. The analysis of micromorphology, element retention and chemical structure character on charring residue, reveals the physical–chemical synergistic carbonization mechanism of NHP/EG composite. The real‐time tracing on thermal‐decomposition volatiles, discloses the behaviors of NHP/EG composite in suppressing volatile fuel supply and toxic fume production. With an addition of 11 wt.% NHP and 7 wt.% EG, 11NHP/7EG achieved a limited oxygen index value of 30.3%, passed horizontal burning class HF‐1, and retained 55.6 wt.% charring residue. The peak of heat release rate and total heat release of 11NHP/7EG were both reduced by more than 50%, compared with that of pristine FPUF. The synergistic flame‐retardant mechanism of NHP/EG composite provides a valuable reference for high‐performance flame‐retardant FPUF manufacturing. [ABSTRACT FROM AUTHOR]

Xylotrechus quadripes (Chevrolat) is the serious woodborer pest of arabica coffee (Coffea arabica L.). To further elucidate the behavior mechanism of the insect based on chemical odorant and to advance effective trapping methods, the typology, distribution, and abundance of antennal sensilla were investigated meticulously in both sexes of X. quadripes by scanning electron microscopy. The filiform antennae of both sexes are composed of 11 segments, namely the scape, pedicel, and nine flagellomeres (f1–9). Ten types (14 subtypes) of sensilla were identified morphologically: sensilla chaetica (three subtypes, Ch.1–3), sensilla basiconica (three subtypes, Ba.1–3), Böhm bristles (Bb), sensilla dentiform (De), sensilla trichodea (Tr), sensilla auricillica (Au), sensilla campaniformia (Ca), grooved peg sensilla (Gp), cuticular pores (Cp), and a newly observed sensillum, named sensilla cone (Cone). The sensilla were mainly distributed in flagellomeres, and the types and amounts increased in frequency from scape to the ninth flagellomere. The numbers of sensilla were the highest on the antennal dorsal side, while the lowest on the ventral side. The types of sensilla were the most abundant on the lateral side, and two sensilla basiconica (Ba.1–2) were found exclusively. The average number of Tr, Ba, and Au on the antenna of the males was significantly greater than females, while the Gp and Cp on the antenna of the females were significantly greater than males. Ca was exclusively occurred on the male antennae but was absent in females. This study discusses the putative functions of the antennal sensilla in adults of X. quadripes based on their characteristics in related species' sensilla, and these results provide an important foundation to clarify the ecological adaption, olfactory recognition mechanism, and to develop the chemical ecology control of X. quadripes. [ABSTRACT FROM AUTHOR]

Background: Alpha oscillations during task switching reveals general attention (low alpha) and higher executive attentional control (high alpha). Alpha oscillations have been related to heart rate variability (HRV), both change in Alzheimer's disease (AD). We aim to explore if task switching challenge with quantitative electroencephalography (qEEG) can reveal abnormal alpha power and HRV in individuals with high risk of AD, and we predict HRV improves qEEG's detection of high AD risk. Method: We compared alpha power during task switching testing between two groups of cognitively healthy participants (52‐91 years) based on different cerebrospinal fluid (CSF) amyloid/tau ratio: normal (CH‐NAT, n=19) or pathological amyloid/tau ratio (CH‐PAT, n=27). Participants were required to name the color or word of a colored word for each stimulus, with two sequential stimuli per trial. Alpha event‐related desynchronization (ERD) was analyzed during low load, repeat trials (color‐color or word‐word) and high load, switch trials (color‐word or word‐color). HRV was assessed from 5‐minute ECG recording during rest or task, including: standard deviation of RR‐intervals (SDNN), root mean squared of successive differences (RMSSD) in the time domain, as well as high (HF) and low frequency (LF) in the frequency domain. We trained a binary classifier to predict the CH‐PATs using a 30 random split of training (80%) and testing (20%) data and two‐layer, fully connected neural network after identifying significant qEEG and HRV features. Result: We found that low alpha power was less negative in CH‐PATs than CH‐NATs (Central: ‐0.18±0.66 vs. ‐0.72±0.72, p=0.011, Cohen's d=0.79; Parietal: ‐0.25±0.75 vs. ‐0.83±0.92, p=0.024, Cohen's d=0.70) (Fig. 1). Furthermore, we observed significant HR and LF changes from resting to task state only in CH‐PATs, but not in CH‐NATs (Fig. 2). After identifying brain features and heart features, we explored the HRV effect on brain features' test accuracy. Conclusion: These results suggest: 1) low alpha power during task switching challenge differs between CH‐PATs and CH‐NATs; 2) HRV suggests hyperactive autonomic regulations from resting to task in CH‐PATs, but not CH‐NATs. qEEG reveals interaction of brain and heart features in early AD pathology that may help early diagnosis and monitoring of novel therapies. [ABSTRACT FROM AUTHOR]

Total synthesis of six natural phenylethanoid glycosides (PhEGs) has been accomplished. Key steps in the divergent synthesis strategy involved glycosylation based on trichloroacetimidate donors, and one‐pot removal of benzyl and 4,6‐O‐benzylidene acetal groups by hydrogenation over Pd/C. Among them, four natural PhEGs, scroside D (2), rebouoside B (3), ginkgoside C (4), and ginkgoside D (5) were synthesized for the first time. In the subsequent antioxidant and tyrosinase inhibitory activities evaluation, all compounds showed strong DPPH radical scavenging activities, and compounds 1–2, 5–6 exhibited obvious inhibitory activities against mushroom tyrosinase. [ABSTRACT FROM AUTHOR]

Background: Little is known about the microbiota and upper gastrointestinal tumors. Esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) occur in adjacent organs, co-occur geographically, and share many risk factors despite being of different tissue types.Methods: This study characterized the microbial communities of paired tumor and nontumor samples from 67 patients with ESCC and 36 patients with GCA in Henan, China. DNA was extracted with the MoBio PowerSoil kit. The V4 region of the 16S ribosomal RNA gene was sequenced with MiniSeq and was processed with Quantitative Insights Into Microbial Ecology 1. The linear discriminant analysis effect size method was used to identify differentially abundant microbes, the Wilcoxon rank-sum test was used to test α diversity differences, and permutational multivariate analysis of variance was used to test for differences in β diversity.Results: The microbial environments of ESCC and GCA tissues were all composed primarily of Firmicutes, Bacteroidetes, and Proteobacteria. ESCC tumor tissues contained more Fusobacterium (3.2% vs 1.3%) and less Streptococcus (12.0% vs 30.2%) than nontumor tissues. GCA nontumor tissues had a greater abundance of Helicobacter (60.5% vs 11.8%), which may have been linked to the lower α diversity (58.0 vs 102.5; P = .0012) in comparison with tumor tissues. A comparison of ESCC and GCA nontumor tissues showed that the microbial composition (P = .0040) and the α diversity (87.0 vs 58.0; P = .00052) were significantly different. No significant differences were detected for α diversity within ESCC and GCA tumor tissues.Conclusions: This study showed differences in the microbial compositions of paired ESCC and GCA tumor and nontumor tissues and differences by organ site. Large-scale, prospective cohort studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Summary: A novel carborane acrylate monomer (1‐acryloyloxyethyl carborane) was synthesized by addition reaction, hydrolysis, and esterification and characterized by proton nuclear magnetic resonance (1H NMR) spectroscopy and Fourier transform infrared spectroscopy (FT‐IR) analysis. Subsequently, the carborane monomer and a phosphate‐containing methacrylate monomer were applied on the modification of a silk fabric. The heat resistance and flame retardancy of the silk fabric before and after modification were compared. Energy‐dispersive X‐ray spectrometer (EDS) and FT‐IR showed that carborane monomer and phosphate‐containing methacrylate were grafted onto the surface of the fibers. The cross‐sectional morphology of silk fabrics after burning was observed by scanning electron microscope (SEM), and the flame‐retardant mechanism was analyzed. Thermal‐gravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis revealed that the thermal stability of the modified silk increased with the increase of the grafting yield. The MCC‐2 microcalorimeter (MCC) test showed that, when using 1‐acryloyloxyethyl carborane as monomer and blending with phosphate‐containing methacrylate, the maximum heat release rate (PHRR) of the modified silk fabric decreased from 97.6 W/g (before grafting) to 51.3 and 45.8 W/g, respectively, and the total heat release (THR) decreased from 10.2 kJ/g (before grafting) to 5.9 and 5.2 kJ/g, respectively. The limiting oxygen index (LOI) test revealed that using 1‐acryloyloxyethyl carborane and phosphate‐containing methacrylate as mixed monomers to modify the silk fabric obtained good flame retardancy, whose LOI value reached 29.8%. [ABSTRACT FROM AUTHOR]

Background: Predicting which patients are most likely to progress to dementia from clinical data remains an open problem with large implications for dementia care. Several predictive models have been developed using volunteer‐based study cohorts; however, practical implementations developed on high‐volume clinical data remain uncommon. Method: We developed a model for predicting whether a patient would receive a dementia diagnosis in one or three years using electronic health record (EHR) data from patients of a US memory clinic. Result: On a held out set of patient data, the developed model had an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% CI: 0.73 – 0.88) and 0.81 (95% CI: 0.68 – 0.91) for predicting dementia within one and three years, respectively. The most predictive clinical features were prior neuropsychiatric and non‐dementia cognitive impairment diagnoses, hospital utilization, and cognitive test scores. Conclusion: While the model's predictive performance is roughly in line with previous studies using longitudinal data, our subsequent analyses highlight the important role of censoring in the development of dementia risk models and the importance of tailoring a model to specific predictive environments. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: Stimuli‐responsive hydrogels crosslinked by weak noncovalent bonds such as hydrogen bonds, ionic interactions, host‐guest interactions and hydrophobic interactions have been extensively investigated. Herein, azobenzene and spiropyran acting as two hydrophobic pendant groups were introduced into a hydrophilic polyacrylamide (PAM) via free radical copolymerization to construct a hydrophobic interaction based thermo‐, light‐ responsive polymer hydrogel. Its viscosity and color could be reversibly regulated by heating and cooling. Meanwhile, its color could be specifically switched by light without obvious viscosity change. The gel was also capable of being transited to sol by addition of β‐cyclodextrin (β‐CD), which encaged the hydrophobic groups and then increased the solubility of polymer in water. The hydrogel could be regained after UV irradiation at λ = 365 nm, and after irradiation at λ = 440 nm, the hydrogel changed into a clear sol again. [ABSTRACT FROM AUTHOR]

The oncoprotein RUNX1–ETO is the fusion product of t(8;21)(q22;q22) and constitutes one of the most common genetic alterations in acute myeloid leukemia (AML). Abnormal c‐KIT overexpression is considered an independent negative prognostic factor for relapse and survival in t(8;21) AML patients. However, the molecular mechanism of high c‐KIT expression in t(8;21) AML remains unknown. In this study, we detected RUNX1–ETO and c‐KIT gene expression in AML‐M2 patients and verified the overexpression of c‐KIT in t(8;21) AML patients. We also found that c‐KIT overexpression was a poor prognostic indicator in RUNX1–ETO positive AML patients, but not in RUNX1–ETO negative AML patients. We used the dual‐luciferase and ChIP assays to demonstrate that the RUNX1–ETO protein epigenetically trans‐activates c‐KIT by binding to the c‐KIT promoter and recruiting the histone acetyltransferase P300 to the c‐KIT promoter, elucidating the mechanism of the abnormally increased c‐KIT expression in t(8;21) AML patients. Moreover, pharmacological studies revealed that C646, a P300 inhibitor, could inhibit proliferation, induce apoptosis and arrest the cell cycle more effectively in RUNX1–ETO positive cells than in negative ones. The levels of c‐KIT and RUNX1–ETO proteins were also decreased with C646 treatment in RUNX1–ETO positive cells. These findings suggested that P300 could be a therapeutic target and that C646 could be used as a potential treatment for RUNX1–ETO positive AML patients. Interestingly, using the dual‐luciferase assay, we also found that the binding capacity of RUNX1–ETO9a, a truncated RUNX1–ETO isoform, to the c‐KIT promoter was stronger than that of RUNX1–ETO, suggesting RUNX1–ETO9a as another valuable therapeutic target in t(8;21) AML. Abnormal c‐KIT overexpression is considered an independent negative prognostic factor in t(8;21) acute myeloid leukemia patients. The RUNX1–ETO/RUNX1–ETO9a protein, the fusion products of t(8;21)(q22;q22), epigenetically trans‐activates c‐KIT by binding to the c‐KIT promoter and recruiting the histone acetyltransferase P300 to the c‐KIT promoter. Moreover, the binding capacity of RUNX1–ETO9a to the c‐KIT promoter was stronger than that of RUNX1–ETO. [ABSTRACT FROM AUTHOR]

In recent years, marine hydrate has attracted more and more attentions. As a creative way to efficiently exploit marine hydrate, the method of solid fluidization exploitation is to excavate and crush hydrate, transport hydrate particles to sea surface platform through airtight pipeline, and obtain methane gas finally. When hydrate particles are transported up, as temperature rises and pressure drops, hydrate will decompose at a certain critical position and produce a large amount of gas, bringing complicated gas‐liquid‐solid multiphase non equilibrium pipe flow, and seriously threating well control securities. Thus, we establish mathematical models of wellbore temperature and pressure, hydrate phase equilibrium, hydrate dynamic decomposition in riser pipe flow and wellbore multiphase flow coupling hydrate dynamic decomposition, and propose and verify numerical calculation method. Then numerical model application analysis under different construction parameters is carried out, influence behaviors of multiphase non equilibrium pipe flow are obtained, and field construction measures are put forward. Properly increasing solid throughput can increase production of natural gas. However, problems such as well control risks will intensify. Therefore, delivery capacity, liquid density, and wellhead back pressure should be increased appropriately at the same time. This study provides important technical support for solid fluidization exploitation of marine hydrate. Physical model and system mathematical models are established to demonstrate multiphase non equilibrium pipe flow in hydrate solid fluidization exploitation of marine natural gas hydrate. Numerical calculation methods for multiphase non equilibrium pipe flow is developed and verified. Numerical model is applied to analyze and obtain the multiphase non equilibrium flow behaviors in hydrate solid fluidization exploitation. [ABSTRACT FROM AUTHOR]

Abstract: Structural studies of the 3′‐end of the oncogenic long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) confirmed a unique triple‐helix structure. This structure enables accumulation of the transcript, and high levels of MALAT1 are found in several cancers. Here, we synthesize a small molecule library based on an RNA‐binding scaffold, diphenylfuran (DPF), screen it against a variety of nucleic acid constructs, and demonstrate for the first time that the MALAT1 triple helix can be selectively targeted with small molecules. Computational analysis revealed a trend between subunit positioning and composition on DPF shape and intramolecular interactions, which in turn generally correlated with selectivity and binding strengths. This work thus provides design strategies toward chemical probe development for the MALAT1 triple helix and suggests that comprehensive analyses of RNA‐focused libraries can generate insights into selective RNA recognition. [ABSTRACT FROM AUTHOR]

Abstract: The prognosis of gastric cancer (GC) remains poor due to clinical drug resistance, and novel drugs are urgently needed. Apoptin‐derived peptide (AdP) is an antitumor polypeptide constructed in our laboratory that has been used to combat cisplatin (CDDP) resistance in GC cells. MTT and colony‐formation assays and Hoechst 33342 staining were used to measure the cytotoxicity of CDDP and AdP in GC cells. Cell apoptosis was measured using an Annexin‐V‐FITC/PI dual staining assay. Western blot analysis was conducted to detect the expression of proteins in the PI3K/AKT signaling pathway and resistance‐related markers. AdP exerted a specific cytotoxic effect on GC cells and CDDP‐resistant GC cells in a concentration‐ and time‐dependent manner. AdP also suppressed cell invasion and migration. Additionally, AdP inhibited the expression of p85, AKT, p‐p85, p‐AKT, multidrug resistance 1 (MDR1), and aryl hydrocarbon nuclear translocator (ARNT) in the PI3K/AKT/ARNT signaling pathway, which promoted apoptosis and necrosis in GC cells. AdP promoted apoptosis in CDDP‐resistant GC cells by suppressing the PI3K/AKT/ARNT signaling pathway and might be considered a candidate agent for the clinical treatment of cisplatin‐resistant GC. [ABSTRACT FROM AUTHOR]

DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)+ AML blasts differs from that of t(8;21)− AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML. Our findings also show that THAP10 is a bona fide target of miR-383 that can be epigenetically activated by the AML1-ETO recruiting co-activator p300. In this study, we demonstrated that epigenetic suppression of THAP10 is the mechanistic link between AML1-ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein that inhibits myeloid proliferation and promotes differentiation both in vitro and in vivo. Altogether, our results revealed an unexpected and important epigenetic mini-circuit of AML1-ETO/THAP10/miR-383 in t(8;21) AML, in which epigenetic suppression of THAP10 predicts a poor clinical outcome and represents a novel therapeutic target. [ABSTRACT FROM AUTHOR]

MicroRNA-9-1( miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines. [ABSTRACT FROM AUTHOR]

Under global warming, a notable intensification of precipitation extremes has posed significant threats to both natural ecosystems and human societies. However, there is still a lack of systematic studies on the variability of hourly precipitation extremes and a comparison with daily precipitation extremes. This study introduces a set of indices for hourly and daily precipitation extremes to systematically examine the changes across eastern China during the summers from 1980 to 2020. The results show that southern China is the sensitive regions with a notable large value of climatology in frequency and intensity for both of hourly and daily precipitation extremes. For the trends, the frequency of hourly precipitation extremes shows a rising trend in southern China, and intensity increased in northern China. Conversely, for daily precipitation extremes, the enhanced intensity and frequency are observed only in southeastern China. Additionally, the eastern coastal area experiences prolonged hourly rainfall with increasing persistence, while the region with an increased duration of daily precipitation is situated further south. Comparing the periods 1980–1999 and 2000–2020, precipitation extremes shift toward more intense and more frequent, with more pronounced variations at the hourly scale. Notably, northeastern China tend to be more intense and shorter‐lived hourly precipitation extremes after 1999, while south China experiences more frequent and longer‐lasting extremes. These changes are partly attributed to the increased unstable conditions, enhanced convective available potential energy and weakened convective inhibition. [ABSTRACT FROM AUTHOR]

Aims: Age‐related bone mass loss is one of the most prevalent diseases that afflict the elderly population. The decline in the osteogenic differentiation capacity of bone marrow‐derived mesenchymal stem cells (BMMSCs) is regarded as one of the central mediators. Voltage‐gated Ca2+ channels (VGCCs) play an important role in the regulation of various cell biological functions, and disruption of VGCCs is associated with several age‐related cellular characteristics and systemic symptoms. However, whether and how VGCCs cause the decreased osteogenic differentiation abilities of BMMSCs have not been fully elucidated. Methods: Voltage‐gated Ca2+ channels related genes were screened, and the candidate gene was determined in several aging models. Functional role of determined channel on osteogenic differentiation of BMMSCs was investigated through gain and loss of function experiments. Molecular mechanism was explored, and intervention experiments in vivo and in vitro were performed. Results: We found that Cav1.2 was downregulated in these aging models, and downregulation of Cav1.2 in Zmpste24−/− BMMSCs contributed to compromised osteogenic capacity. Mechanistically, Cav1.2 regulated the osteogenesis of BMMSCs through canonical Wnt/β‐catenin pathway. Moreover, upregulating the activity of Cav1.2 mitigated osteoporosis symptom in Zmpste24−/− mice. Conclusion: Impaired osteogenic differentiation of Zmpste24−/− BMMSCs can be partly attributed to the decreased Cav1.2 expression, which leads to the inhibition of canonical Wnt pathway. Bay K8644 treatment could be an applicable approach for treating age‐related bone loss by ameliorating compromised osteogenic differentiation capacity through targeting Cav1.2 channel. [ABSTRACT FROM AUTHOR]

Aims: Age-related bone mass loss is one of the most prevalent diseases that afflict the elderly population. The decline in the osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMMSCs) is regarded as one of the central mediators. Voltage-gated Ca 2+ channels (VGCCs) play an important role in the regulation of various cell biological functions, and disruption of VGCCs is associated with several age-related cellular characteristics and systemic symptoms. However, whether and how VGCCs cause the decreased osteogenic differentiation abilities of BMMSCs have not been fully elucidated., Methods: Voltage-gated Ca 2+ channels related genes were screened, and the candidate gene was determined in several aging models. Functional role of determined channel on osteogenic differentiation of BMMSCs was investigated through gain and loss of function experiments. Molecular mechanism was explored, and intervention experiments in vivo and in vitro were performed., Results: We found that Ca v 1.2 was downregulated in these aging models, and downregulation of Ca v 1.2 in Zmpste24-/- BMMSCs contributed to compromised osteogenic capacity. Mechanistically, Ca v 1.2 regulated the osteogenesis of BMMSCs through canonical Wnt/β-catenin pathway. Moreover, upregulating the activity of Ca v 1.2 mitigated osteoporosis symptom in Zmpste24-/- mice., Conclusion: Impaired osteogenic differentiation of Zmpste24-/- BMMSCs can be partly attributed to the decreased Ca v 1.2 expression, which leads to the inhibition of canonical Wnt pathway. Bay K8644 treatment could be an applicable approach for treating age-related bone loss by ameliorating compromised osteogenic differentiation capacity through targeting Ca v 1.2 channel., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)