Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress.

Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast (Schizosaccharomyces pombe). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1Cdc20, the co-activator of APC/C. Phosphorylation of Slp1Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells.

Inland water greenhouse gas emissions offset the terrestrial carbon sink in the northern cryosphere.

Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide ([Formula: see text] teragrams of CO2; [Formula: see text]) and methane ([Formula: see text] teragrams of CH4), while the nitrous oxide emission ([Formula: see text] gigagrams of N2O) is minor. The annual CO2-equivalent (CO2e) GHG emissions from northern cryosphere inland waters total [Formula: see text] or [Formula: see text] petagrams of CO2e using the 100- or 20-year global warming potentials, respectively. Rivers emit 64% more CO2e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO2e emissions from northern cryosphere inland waters exceed the region's terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate.

Soil water dynamics and plant water uptake: Primeval mature vs. debris flow-developed half-mature subalpine fir stands in the eastern Tibetan Plateau.

Natural disaster can disrupt soil structure and replace established vegetation with younger plants, altering the local hydrological processes. We used hydrogen and oxygen stable isotopes to examine soil water dynamics and plant water uptake patterns in two adjacent fir stands in the eastern Qinghai-Tibet Plateau: a primeval mature stand (MF, finer- textured soil) and a debris flow-developed half-mature stand (HMF, coarser-textured soil). Our results showed that the isotopic composition and soil gravimetric water content (SWC) in deep soil water in MF exhibited a more pronounced hysteresis pattern in response to precipitation compared to HMF, indicating lower turnover rate of soil water in MF. This was also confirmed by a smaller contribution of preferential flow to deep soil water in MF compared to HMF. The higher water storage (higher SWC values) and lower turnover rate of soil water suggest a higher soil water buffer capacity in MF. Additionally, both stands showed no significant difference in plant water sources, but plants in MF used more winter precipitation due to the lower soil water turnover rate. These differences suggest MF may be more vulnerable to water disasters, while HMF may be more susceptible to seasonal droughts under climate change. Our insights enhance understanding of hydrological processes linked to changing surface conditions and offer valuable information for managing forest water resources in mountainous regions.

Pre-operative prediction of histopathological growth patterns of colorectal cancer liver metastasis using MRI-based radiomic models.

PURPOSE: Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLMs) have prognostic value. However, the differentiation of HGPs relies on postoperative pathology. This study aimed to develop a magnetic resonance imaging (MRI)-based radiomic model to predict HGP pre-operatively, following the latest guidelines. METHODS: This retrospective study included 93 chemotherapy-naïve patients with CRLMs who underwent contrast-enhanced liver MRI and a partial hepatectomy between 2014 and 2022. Radiomic features were extracted from the tumor zone (RTumor), a 2-mm outer ring (RT+2), a 2-mm inner ring (RT-2), and a combined ring (R2+2) on late arterial phase MRI images. Analysis of variance method (ANOVA) and least absolute shrinkage and selection operator (LASSO) algorithms were used for feature selection. Logistic regression with five-fold cross-validation was used for model construction. Receiver operating characteristic curves, calibrated curves, and decision curve analyses were used to assess model performance. DeLong tests were used to compare different models. RESULTS: Twenty-nine desmoplastic and sixty-four non-desmoplastic CRLMs were included. The radiomic models achieved area under the curve (AUC) values of 0.736, 0.906, 0.804, and 0.794 for RTumor, RT-2, RT+2, and R2+2, respectively, in the training cohorts. The AUC values were 0.713, 0.876, 0.785, and 0.777 for RTumor, RT-2, RT+2, and R2+2, respectively, in the validation cohort. RT-2 exhibited the best performance. CONCLUSION: The MRI-based radiomic models could predict HGPs in CRLMs pre-operatively.

The impact of extreme precipitation on water use efficiency along vertical vegetation belts in Hengduan Mountain during 2001 and 2020.

In the context of climate change, extreme precipitation events are continuously increasing and impact the water­carbon coupling of ecosystems. The vertical vegetation zonation, as a characteristic of mountain ecosystems, reflects the differences in vegetation response to climate change at different elevations. In this study, we used the water use efficiency (WUE) as an indicator to evaluate the water­carbon relationship. By using MODIS data, we analyzed the spatiotemporal patterns of gross primary productivity (GPP), evapotranspiration (ET), and WUE from 2001 to 2020, as well as the responses of WUE to extreme wetness factor Number of precipitation days (R0.1), extreme dryness factor Consecutive dry days (CDD), and meteorological factors under the vertical vegetation zonation. Our results showed that annual GPP and ET displayed a significant increasing trend between 2001 and 2020, whereas WUE showed a weak decreasing trend. Spatially, GPP and WUE decreased with increasing elevation. Analyzing the WUE of mountainous ecosystems as a unified whole may not precisely capture the reactions of vegetation to severe rainfall occurrences. In fact, across different vegetation belts in mountainous areas, there exists a negative correlation between WUE and R0.1, and a positive correlation with CDD. In terms of meteorological factors, the temporal variation of GPP was primarily associated with vapor pressure deficit (VPD) and temperature (Ta), while those of ET was mainly related to soil water content (SWC). WUE was affected by a combination of meteorological factors and had a certain degree of variation between different altitude intervals. These findings contribute to a better understanding and prediction of the relationship between extreme rainfall climate and water­carbon coupling in mountainous areas.

Flexoelectric Engineering of Bulk Photovoltaic Photodetector.

The bulk photovoltaic effect (BPVE) offers an interesting approach to generate a steady photocurrent in a single-phase material under homogeneous illumination, and it has been extensively investigated in ferroelectrics exhibiting spontaneous polarization that breaks inversion symmetry. Flexoelectricity breaks inversion symmetry via a strain gradient in the otherwise nonpolar materials, enabling manipulation of ferroelectric order without an electric field. Combining these two effects, we demonstrate active mechanical control of BPVE in suspended 2-dimensional CuInP2S6 (CIPS) that is ferroelectric yet sensitive to electric field, which enables practical photodetection with an order of magnitude enhancement in performance. The suspended CIPS exhibits a 20-fold increase in photocurrent, which can be continuously modulated by either mechanical force or light polarization. The flexoelectrically engineered photodetection device, activated by air pressure and without any optimization, possesses a responsivity of 2.45 × 10-2 A/W and a detectivity of 1.73 × 1011 jones, which are superior to those of ferroelectric-based photodetection and comparable to those of the commercial Si photodiode.

Increased Deep Trap Density in Interfacial Engineered Nanocomposite Revealed by Sequential Kelvin Probe Force Microscopy for High Dielectric Energy Storage.

Nanocomposites combining inorganic nanoparticles with high dielectric constant and polymers with high breakdown strength are promising for the high energy density storage of electricity, and carrier traps can significantly affect the dielectric breakdown process. Nevertheless, there still lacks direct experimental evidence on how nanoparticles affect the trap characteristics of nanocomposites, especially in a spatially resolved manner. Here, a technique is developed to image the trap distribution based on sequential Kelvin probe force microscopy (KPFM) in combination with the isothermal surface potential decay (ISPD) technique, wherein both shallow and deep trap densities and the corresponding energy levels can be mapped with nanoscale resolution. The technique is first validated using the widely-used commercial biaxially oriented polypropylene, yielding consistent results with macroscopic ISPD. The technique is then applied to investigate polyvinylidene fluoride-based nanocomposites filled with barium titanate nanoparticles, revealing higher deep trap density around surface-modified nanoparticles, which correlates well with its increased breakdown strength. This technique thus provides a powerful spatially resolved tool for understanding the microscopic mechanism of dielectric breakdown of nanocomposites.

Nitrogen dynamics of alpine swamp meadows are less responsive to climate warming than that of alpine meadows.

The freeze-thaw cycle mediates permafrost soil hydrothermal status, nitrogen (N) mineralization, and loss. Furthermore, it affects root development and competition among nitrophilic and other species, shaping the pattern of N distribution in alpine ecosystems. However, the specific N dynamics during the growing season and N loss during the non-growing season in response to climate warming under low- and high-moisture conditions are not well documented. Therefore, we added 15N tracers to trace the fate of N in warmed and ambient alpine meadows and alpine swamp meadows in the permafrost region of the Qinghai-Tibet Plateau. During the growing season, warming increased 15N recovery (15Nrec) in shoots of K. humilis, litters, 0-5 and 5-20 cm roots in the alpine meadow by 149.94 % ± 52.87 %, 114.58 % ± 24.43 %, 61.11 % ± 32.27 %, and 97.12 % ± 42.92 %, respectively, while increased 15Nrec of litters by 151.55 % ± 27.06 % in the alpine swamp meadow. During the non-growing season, warming reduced 15N stored in roots by 486.77 % ± 57.90 %, though increased the 15N recovery in 5-20 cm soil depth by 76.68 % ± 39.42 % in the alpine meadow, whereas it did not affect N loss during the non-growing season in the alpine swamp meadow. Overall, warming promoted N utilization by increasing the plant N pool during the growing season, and enhanced root N loss and downward migration during the non-growing season due to the freeze-thaw process, which may result in fine root turnover and cell destruction releasing N in the alpine meadow. Conversely, the N dynamics of alpine swamp meadows were less responsive to climate warming.

Escaping from CRISPR-Cas-mediated knockout: the facts, mechanisms, and applications.

Clustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR-Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR-Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR-Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR-Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.

Hydroxamate-Containing Bisphosphonates as Fosmidomycin Analogues: Design, Synthesis, and Proherbicide Activity.

Fosmidomycin (FOS) is a natural product inhibiting the DXR enzyme in the MEP pathway and has stimulated interest for finding more suitable FOS analogues. Herein, two series of FOS analogue hydroxamate-containing bisphosphonates as proherbicides were designed, with bisphosphonate replacing the phosphonic unit in FOS while retaining the hydroxamate (BPF series) or replacing it with retro-hydroxamate (BPRF series). The BPF series were synthesized through a three-step reaction sequence including Michael addition of vinylidenebisphosphonate, N-acylation, and deprotection, and the BPRF series were synthesized with a retro-Claisen condensation incorporated into the reaction sequence. Evaluation on model plants demonstrated several compounds having considerable herbicidal activities, and in particular, compound 8m exhibited multifold activity enhancement as compared to the control FOS. The proherbicide properties were comparatively validated. Furthermore, DXR enzyme assay, dimethylallyl pyrophosphate rescue, and molecular docking verified 8m to be a promising proherbicide candidate targeting the DXR enzyme. In addition, 8m also displayed good antimalarial activities.

The seasonal variability of future evapotranspiration over China during the 21st century.

The evapotranspiration (ET) plays a crucial role in shaping regional climate patterns and serves as a vital indicator of ecosystem function. However, there remains a limited understanding of the seasonal variability of future ET over China and its correlation with environmental drivers. This study evaluated the skills of 27 models from the Six Phase of Coupled Model Intercomparison Project in modeling ET and the Bayesian Model Averaging (BMA) method was employed to merge monthly simulated ET based on the top five best-performing models. The seasonal changes in ET under three climate scenarios from 2030 to 2099 were analyzed based on the BMA-merged ET, which was well validated with observed ET collected from fourteen flux sites across China. Significant increasing ET over China are projected under all seasons during 2030-2099, with 0.05-0.13 mm yr-1, 0.11-0.23 mm yr-1, and 0.20-0.41 mm yr-1 under SSP1-2.6, SSP2-4.5 and SSP5-8.5 scenarios, respectively. Relative to the historical period (1980-2014), the relative increase in ET over China is highest in winter and lowest in summer. Seasonal ET increases significantly in all seven climate sub-regions under high forcing scenario. Higher ET increase is generally found in southeastern humid regions, while lowest ET increase occurs in northwest China. At the country level, the primary factor driving ET increase during spring, summer, and autumn seasons is the increasing net radiation and warming. In contrast, ET increase during winter is influenced not only by energy factors but also by vegetation-related factors. Future seasonal ET increase is predominantly driven by increasing energy factors in the southeastern humid region and Tibetan Plateau, while seasonal ET changes in the northwest region prevailingly depend on soil moisture. Results indicate that China will experience a "wet season will get wetter, and dry season will become drier" in the 21st century with high radiation forcing scenario.

Surfactant-assisted preparation of all-gel-state flexible supercapacitor with remarkable electrochemical performance based on polyaniline-polyacrylamide/sodium alginate hydrogels.

The electrochemical performance of polyaniline-based all-gel-state supercapacitor (AGSSC) is significantly depended on the dispersity and mass loaded of polyaniline (PANI). In this manuscript, inspired by the properties of surfactant, sodium dodecylbenzene sulfonate (SDBS) was introduced to prepare various PANI-polyacrylamide/sodium alginate/SDBS (PANIy-PSSx) AGSSCs. With presence of SDBS, the electrochemical performance of PANIy-PSSx AGSSCs was greatly improved, displaying a trend of initial rise and then decrease with increasing concentration of SDBS from 0 to 0.75 wt%. As the content of SDBS was 0.5 wt%, the resulting PANI1.0-PSS0.5 AGSSC displayed the optimum electrochemical properties with area capacitance and energy density of 913.79 mF/cm2 and 81.23 µWh/cm2, respectively. The capacitance rate of PANI1.0-PSS0.5 AGSSC was still more than 93 % after 2000 cycles of sequential CV scans at the scan rate of 200 mV/s. These data were greatly higher than many reported PANI-based AGSSCs. Moreover, the resultant PANI1.0-PSS0.5 AGSSC could maintain high electrochemical performance even after various operations, such as compression, puncture, fluctuating temperature, bending situations and various voltage windows and series-parallel connections. The resultant PANI1.0-PSS0.5 AGSSC had the wide potentials to satisfy the real application requirements. This study offered a facile strategy for design and preparation of flexible supercapacitor with excellent electrochemical performance.

Functional analysis of Cdc20 reveals a critical role of CRY box in mitotic checkpoint signaling.

Accurate mitosis is coordinated by the spindle assembly checkpoint (SAC) through the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex or cyclosome (APC/C). As an essential regulator, Cdc20 promotes mitotic exit through activating APC/C and monitors kinetochore-microtubule attachment through activating SAC. Cdc20 requires multiple interactions with APC/C and MCC subunits to elicit these functions. Functionally assessing these interactions within cells requires efficient depletion of endogenous Cdc20, which is highly difficult to achieve by RNA interference (RNAi). Here we generated Cdc20 RNAi-sensitive cell lines which display a penetrant metaphase arrest by a single RNAi treatment. In this null background, we accurately measured the contribution of each known motif of Cdc20 on APC/C and SAC activation. The CRY box, a previously identified degron, was found critical for SAC by promoting MCC formation and its interaction with APC/C. These data reveal additional regulation within the SAC and establish a novel method to interrogate Cdc20.

Heat stress-induced activation of MAPK pathway attenuates Atf1-dependent epigenetic inheritance of heterochromatin in fission yeast.

Eukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeast Schizosaccharomyces pombe, heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type (mat) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at the mat locus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of mitogen-activated protein kinase (MAPK) signaling disrupts epigenetic maintenance of heterochromatin at the mat locus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6HP1, resulting in lower site-specific Swi6HP1 enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6HP1 to the mat3M-flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at the mat locus.

Recent intensified erosion and massive sediment deposition in Tibetan Plateau rivers.

Recent climate change has caused an increase in warming-driven erosion and sediment transport processes on the Tibetan Plateau (TP). Yet a lack of measurements hinders our understanding of basin-scale sediment dynamics and associated spatiotemporal changes. Here, using satellite-based estimates of suspended sediment, we reconstruct the quantitative history and patterns of erosion and sediment transport in major headwater basins from 1986 to 2021. Out of 13 warming-affected headwater regions, 63% of the rivers have experienced significant increases in sediment flux. Despite such intensified erosion, we find that 30% of the total suspended sediment flux has been temporarily deposited within rivers. Our findings reveal a pronounced spatiotemporal heterogeneity within and across basins. The recurrent fluctuations in erosion-deposition patterns within river channels not only result in the underestimation of erosion magnitude but also drive continuous transformations in valley morphology, thereby endangering local ecosystems, landscape stability, and infrastructure project safety.

Design and synthesis of fosmidomycin analogs containing aza-linkers and their biological activity evaluation.

BACKGROUND: The enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway are attractive targets of a new mode of action for developing anti-infective drugs and herbicides, and inhibitors against 1-deoxy-d-xylulose 5-phosphate reductoisomerase (IspC), the second key enzyme in the pathway, have been intensively investigated; however, few works are reported regarding IspC inhibitors designed for new herbicide discovery. RESULTS: A series of fosmidomycin (FOS) analogs were designed with nitrogen-containing linkers replacing the trimethylene linker between the two active substructures of FOS, phosphonic acid and hydroxamic acid. Synthesis followed a facile three-step route of sequential aza-Michael addition of α-amino acids to dibenzyl vinylphosphonate, amidation of the amino acid carboxyl with O-benzyl hydroxylamine, and simultaneous removal of the benzyl protective groups. Biological activity evaluation of IspC and model plants revealed that some compounds had moderate enzyme and model plant growth inhibition effects. In particular, compound 10g, which has a N-(4-fluorophenylethyl) nitrogen-containing linker, exhibited the best plant inhibition activities, superior to the control FOS against the model plants Arabidopsis thaliana, Brassica napus L., Amaranthus retroflexus and Echinochloa crus-galli. A dimethylallyl pyrophosphate rescue assay on A. thaliana confirmed that both 10g and FOS exert their herbicidal activity by blocking the MEP pathway. This result consistent with molecular docking, which confirmed 10g and FOS binding to the IspC active site in a similar way. CONCLUSION: Compound 10g has excellent herbicidal activity and represents the first herbicide lead structure of a new mode of action that targets IspC enzyme in the MEP pathway. © 2023 Society of Chemical Industry.

The optimized Fenton-like activity of Fe single-atom sites by Fe atomic clusters-mediated electronic configuration modulation.

The performance optimization of isolated atomically dispersed metal active sites is critical but challenging. Here, TiO2@Fe species-N-C catalysts with Fe atomic clusters (ACs) and satellite Fe-N4 active sites were fabricated to initiate peroxymonosulfate (PMS) oxidation reaction. The AC-induced charge redistribution of single atoms (SAs) was verified, thus strengthening the interaction between SAs and PMS. In detail, the incorporation of ACs optimized the HSO5- oxidation and SO5·- desorption steps, accelerating the reaction progress. As a result, the Vis/TiFeAS/PMS system rapidly eliminated 90.81% of 45 mg/L tetracycline (TC) in 10 min. The reaction process characterization suggested that PMS as an electron donor would transfer electron to Fe species in TiFeAS, generating 1O2. Subsequently, the hVB+ can induce the generation of electron-deficient Fe species, promoting the reaction circulation. This work provides a strategy to construct catalysts with multiple atom assembly-enabled composite active sites for high-efficiency PMS-based advanced oxidation processes (AOPs).

Generating dual-active species by triple-atom sites through peroxymonosulfate activation for treating micropollutants in complex water.

The peroxymonosulfate (PMS)-triggered radical and nonradical active species can synergistically guarantee selectively removing micropollutants in complex wastewater; however, realizing this on heterogeneous metal-based catalysts with single active sites remains challenging due to insufficient electron cycle. Herein, we design asymmetric Co-O-Bi triple-atom sites in Co-doped Bi2O2CO3 to facilitate PMS oxidation and reduction simultaneously by enhancing the electron transfer between the active sites. We propose that the asymmetric Co-O-Bi sites result in an electron density increase in the Bi sites and decrease in the Co sites, thereby PMS undergoes a reduction reaction to generate SO4•- and •OH at the Bi site and an oxidation reaction to generate 1O2 at the Co site. We suggest that the synergistic effect of SO4•-, •OH, and 1O2 enables efficient removal and mineralization of micropollutants without interference from organic and inorganic compounds under the environmental background. As a result, the Co-doped Bi2O2CO3 achieves almost 99.3% sulfamethoxazole degradation in 3 min with a k-value as high as 82.95 min-1 M-1, which is superior to the existing catalysts reported so far. This work provides a structural regulation of the active sites approach to control the catalytic function, which will guide the rational design of Fenton-like catalysts.

Enhanced Interfacial Electron Transfer by Asymmetric Cu-Ov -In Sites on In2 O3 for Efficient Peroxymonosulfate Activation.

Enhancing the peroxymonosulfate (PMS) activation efficiency to generate more radicals is vital to promote the Fenton-like reaction activity, however, how to promote the PMS adsorption and accelerate the interfacial electron transfer to boost its activation kinetics remains a great challenge. Herein, we prepared Cu-doped defect-rich In2 O3 (Cu-In2 O3 /Ov ) catalysts containing asymmetric Cu-Ov -In sites for PMS activation in water purification. The intrinsic catalytic activity is that the side-on adsorption configuration of the O-O bond (Cu-O-O-In) at the Cu-Ov -In sites significantly stretches the O-O bond length. Meanwhile, the Cu-Ov -In sites increase the electron density near the Fermi energy level, promoting more and faster electron transfer to the O-O bond for generating more SO4 ⋅- and ⋅OH. The degradation rate constant of tetracycline achieved by Cu-In2 O3 /Ov is 31.8 times faster than In2 O3 /Ov , and it shows the possibility of membrane reactor for practical wastewater treatment.