StratoLAMP: Label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of precipitate.

Multiplex, digital nucleic acid detections have important biomedical applications, but the multiplexity of existing methods is predominantly achieved using fluorescent dyes or probes, making the detection complicated and costly. Here, we present the StratoLAMP for label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of the precipitate byproduct. The StratoLAMP designates two sets of primers with different concentrations to achieve different precipitate yields when amplifying different nucleic acid targets. In the detection, deep learning image analysis is used to stratify the precipitate within each droplet and determine the encapsulated targets for nucleic acid quantification. We investigated the effect of the amplification reagents and process on the precipitate generation and optimized the assay conditions. We then implemented a deep-learning image analysis pipeline for droplet detection, achieving an overall accuracy of 94.3%. In the application, the StratoLAMP successfully achieved the simultaneous quantification of two nucleic acid targets with high accuracy. By eliminating the need for fluorescence, StratoLAMP represents a unique concept toward label-free, multiplex nucleic acid assays and an analytical tool with great cost-effectiveness.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Ecosystem multifunctionality is more related to the indirect effects than to the direct effects of human management in China's drylands.

Drylands provide a wide range of important ecosystem functions but are sensitive to environmental changes, especially human management. Two major land use types of drylands are grasslands and croplands, which are influenced by intensive grazing activities and agricultural management, respectively. However, little is known about whether the ecosystem functioning of these two land use types is predominated affected by human management, or environmental factors (intrinsic environmental factors and factors modified by human management). This limits our understanding of the ecosystem functions under intensive human management in drylands. Here we reported a study where we collected data from 40 grassland and 30 cropland sites along an extensive aridity gradient in China's drylands to quantify the effects of human management intensity, intrinsic environmental factors (i.e., aridity), and environmental factors modified by human management (i.e., soil bulk density and plant density) on specific ecosystem functions (ecosystem multifunctionality, productivity, carbon storage, soil water, and soil nutrients). We found that the relative importance of each function differed between croplands and grasslands. Ecosystem functions varied with human management intensity, with lower productivity and plant carbon storage in grasslands under high grazing intensity than un-grazed, while multifunctionality and carbon storage increased with greater fertilization only in arid croplands. Furthermore, among environmental factors, soil bulk density had the greatest negative effects, which directly reduced multifunctionality in grasslands and indirectly reduced multifunctionality in croplands via suppressing crop density. Crop density was the major environmental factor that positively related to multifunctionality in croplands. However, these effects would be exacerbated with increasing aridity. Our study demonstrated that compared with the direct impacts of human management, environmental factors modified by human management (e.g., soil bulk density) are the major drivers of ecosystem functions, indicating that improving soil structure by alleviating human interferences (e.g., reducing livestock trampling) would be an effective way to restore ecosystem functions in drylands under global warming and drying.

Heterogeneity changes of active bacterial community on cigar filler leaves after fermentation based on metagenome.

Microorganisms play an important role in cigar fermentation. To further explore the dynamic changes of bacterial community composition, the changes of surface bacterial diversity of cigar filler leaves were investigated in the present study by high-throughput sequencing technology. It was found that the surface bacterial richness was declined after fermentation, and the dominant microorganisms on the surface of cigar filler leaves evolved from Pseudomonas spp. and Sphingomonas spp. before fermentation to Staphylococcus spp. after fermentation. The chemical composition and sensory quality evaluation of cigar filler leaves were closely related to the changes of surface bacterial community. The changes of the dominant surface bacterial community led to the differences of metabolic functions, among which the metabolic pathways such as the synthesis of secondary metabolites, carbon metabolism, and amino acid biosynthesis were significantly different. The results provide a basis for clarifying the roles of bacteria in fermentation of cigar filler leaves.

Divergent responses of ecosystem services to afforestation and grassland restoration in the Tibetan Plateau.

Afforestation and grassland restoration have been proposed as important pathways for nature-based solutions. However, the effects of different ecological restoration projects on multiple ecosystem services are poorly understood, inhibiting our ability to maximize ecosystem services for further restoration. Here, we provide a comprehensive assessment of the impact of different ecological projects on ecosystem services (carbon storage, water conservation, soil retention), using a pairwise comparative study of samples from 90 project-control pairs in the Tibetan Plateau. Our results found that afforestation increased carbon storage (31.3%) and soil retention (37.6%), but the effects of grassland restoration on services were mixed, while the overall changes in water conservation were negligible. Prior land use/measures and the age of project implementation were key factors in regulating ecosystem service responses. For example, afforestation on bare land increased carbon storage and soil retention but indirectly decreased water conservation by influencing vegetation cover, while cropland afforestation increased water and soil retention. Ecosystem services increased with project age after afforestation. For grassland restoration, short-term recovery increased carbon storage but was not effective in improving water and soil retention. Climate and topography also directly or indirectly controlled the response of ecosystem services by affecting the changes in total nitrogen, total porosity, clay and fractional vegetation cover following the projects. This study improves our current understanding of the mechanisms underlying the responses of ecosystem services to afforestation and grassland restoration. Our results suggest that sustainable restoration management taking into account prior land use/measures, implementation age, climate, topography and other resources is critical for optimizing ecosystem services.

Plant functional traits explain long-term differences in ecosystem services between artificial forests and natural grasslands.

Declining ecosystem services have prompted numerous studies aiming at developing more sustainable management practices for vegetation restoration. Advances in functional ecology indicate that the sustainable management of afforestation ecosystems should be performed based on plant functional traits, which provides pivotal knowledge for long-term sustainable vegetation restoration. Currently, the mechanism of how plant functional traits affect long term ecosystem services in restored areas is still unclear. This study investigates plant functional traits and the associated ecosystem services from artificial forestlands (Robinia pseudoacacia, Caragana korshinskii) and natural grasslands following different durations of vegetation restoration (10, 20, 30 and 40 years) in the Danangou watershed, a loess hilly-gully region in the Loess Plateau, China. The results showed that 1) the water conservation services of artificial forestlands first decreased and then increased over time, whereas the soil conservation service had an opposite trend; in turn, natural grassland led to a consistent increase in soil conservation and carbon sequestration services over time. 2) Artificial forestlands had greater soil conservation and carbon sequestration services than natural grassland but had lower water conservation services. 3) Leaves had a greater impact on carbon sequestration and water conservation services than did root length and root biomass density. 4) Root biomass density had a greater effect on soil conservation services than did leaf carbon content and soil organic matter. 5) Leaf carbon content, specific root length, and root biomass density had significant effects on the trade-off value between any two ecosystem services with increasing time after restoration of artificial forestland. 6) Specific leaf area had a greater effect on the trade-off values among the three services than did the other functional traits in the natural grassland. In arid ecosystems, natural grasslands are the best restoration strategy given their higher water conservation services. However, in soil erosion-affected areas, restoration through artificial forestlands is more appropriate. To mitigate the trade-offs between ecosystem services, it is recommended that artificial forestlands be thinned before the leaf carbon content, specific root length, and root biomass density reach a maximum (i.e., mature forestland).

Roadside verges support greater ecosystem functions than adjacent agricultural land in a grassy woodland.

Vegetation clearance is the major land use change in agricultural landscape, where woody species are removed to support agricultural production. Native woody species are now largely restricted to the thin strips along the road (roadside verges). Despite the importance of roadside verges as refugia for native species, their impacts on ecological functions and the driving factors have been little explored over extensive areas, limiting our capacity to argue for the retention and improvement of these 'off-reserve' habitats within agroecosystems. We compared the magnitude of ecological functions between paired roadside verges and adjacent agricultural land at 111 sites along a vegetation condition gradient in eastern Australia to examine the ecological importance of roadside verges and the potential regulators. Eighty-six percent of our 21 ecological attributes differed between roadsides and adjacent agricultural land, with roadside verges supporting greater carbon stocks, vegetation coverage, plant diversity, habitat complexity and tree recruitment, and were subject to less modification and erosion. These ecological effects strengthened with increasing roadside verge width, particularly for plant cover and diversity, the proportion of native plant species and habitat complexity. Management practices were major regulators of roadside functions, with roadside verge width and site modification negatively associated with tree recruitment and the soil organic carbon pool. Site modification and roadside verge width also indirectly reduced the soil organic carbon pool by either suppressing tree diversity or promoting the proportion of native plant species. Our study provides empirical evidence of the ecological importance of roadside verges in maintaining ecosystem functions and the sustainability of native plant communities in peri-agricultural landscapes. Our study also demonstrates the negative effects of site modification on tree recruitment and soil organic carbon pools, highlighting the importance of mitigating management activities (e.g., tree removal, fire, grazing) in the conservation of roadside verges.

KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP.

Hepatocellular carcinoma (HCC) is a prevalent solid cancer worldwide and sorafenib is a common treatment. Nevertheless, sorafenib resistance is a severe clinical problem. In the present study, we identified that epigenetic regulator, KAT6A, was overexpressed in clinical HCC tissues and sorafenib-resistant HCC samples. The depletion of KAT6A repressed the cell viability and Edu-positive cell numbers of HCC cells. The IC50 value of sorafenib was increased in sorafenib-resistant HCC cells. In addition, the expression of KAT6A was induced in sorafenib-resistant HCC cells. The depletion of KAT6A suppressed the IC50 of sorafenib. Mechanically, YAP was decreased by the depletion of KAT6A. KAT6A was able to enrich in the promoter of YAP. The silencing of KAT6A reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) and RNA polymerase II (RNA pol II) on the promoter of YAP in sorafenib-resistant HCC cells. KAT6A inhibitor WM-1119 repressed the cell proliferation of sorafenib-resistant HCC cells, while overexpression of KAT6A or YAP could reverse the effect in the cells. Meanwhile, the treatment of sorafenib inhibited the viability of sorafenib-resistant HCC cells, while the co-treatment of WM-1119 could improve the effect of sorafenib. Collectively, KAT6A was associated with sorafenib resistance and contributes to progression of HCC by targeting YAP. Targeting KAT6A may be served as a promising therapeutic approach for HCC.

Remove or retain: ecosystem effects of woody encroachment and removal are linked to plant structural and functional traits.

The impacts of woody encroachment and removal on ecosystems are highly variable and are thought to be related to the traits of the individual woody species. Decisions on whether to remove or to retain woody plants are hampered by a lack of empirical evidence of the relationship between woody traits and the ecosystem consequences of their removal or retention. We used a global meta-analysis of 149 ecosystem attributes from 172 woody species to evaluate the relative effects of woody plant traits and abiotic environmental variables on the ecosystem consequences of woody encroachment and removal. The ecosystem consequences were closely related to woody plant traits. For example, encroachment of plants characterized by high structural traits (e.g. tall, mixed tap and fibrous roots) reduced ecosystem composition, while removal of plants characterized by high functional traits (e.g. nitrogen fixing, deciduous) reduced ecosystem function. Structural and functional traits of woody plants mainly regulated soil stability during woody encroachment and herbaceous cover after woody removal. Conversely, environmental conditions mainly affected herbaceous cover under encroachment and soil stability under removal scenarios. We demonstrate that the ecosystem consequences of encroachment and removal are closely linked to the structural and functional traits of the target woody species. Furthermore, biotic (woody plant traits) and abiotic (climate, soils) factors have different impacts on regulating trade-offs between ecosystem responses under these two management scenarios. Our study provides empirical support for management decisions on whether to retain or remove different woody taxa under various environments across the globe.

Multiple trade-offs regulate the effects of woody plant removal on biodiversity and ecosystem functions in global rangelands.

Woody plant encroachment is a major land management issue. Woody removal often aims to restore the original grassy ecosystem, but few studies have assessed the role of woody removal on ecosystem functions and biodiversity at global scales. We collected data from 140 global studies and evaluated how different woody plant removal methods affected biodiversity (plant and animal diversity) and ecosystem functions (plant production, hydrological function, soil carbon) across global rangelands. Our results indicate that the impact of removal is strongly context dependent, varying with the specific response variable, removal method, and traits of the target species. Over all treatments, woody plant removal increased grass biomass and total groundstorey diversity. Physical and chemical removal methods increased grass biomass and total groundstorey biomass (i.e., non-woody plants, including grass biomass), but burning reduced animal diversity. The impact of different treatment methods declined with time since removal, particularly for total groundstorey biomass. Removing pyramid-shaped woody plants increased total groundstorey biomass and hydrological function but reduced total groundstorey diversity. Environmental context (e.g., aridity and soil texture) indirectly controlled the effect of removal on biomass and biodiversity by influencing plant traits such as plant shape, allelopathic, or roots types. Our study demonstrates that a one-size-fits-all approach to woody plant removal is not appropriate, and that consideration of woody plant identity, removal method, and environmental context is critical for optimizing removal outcomes. Applying this knowledge is fundamental for maintaining diverse and functional rangeland ecosystems as we move toward a drier and more variable climate.

The pervasive and multifaceted influence of biocrusts on water in the world's drylands.

The capture and use of water are critically important in drylands, which collectively constitute Earth's largest biome. Drylands will likely experience lower and more unreliable rainfall as climatic conditions change over the next century. Dryland soils support a rich community of microphytic organisms (biocrusts), which are critically important because they regulate the delivery and retention of water. Yet despite their hydrological significance, a global synthesis of their effects on hydrology is lacking. We synthesized 2,997 observations from 109 publications to explore how biocrusts affected five hydrological processes (times to ponding and runoff, early [sorptivity] and final [infiltration] stages of water flow into soil, and the rate or volume of runoff) and two hydrological outcomes (moisture storage, sediment production). We found that increasing biocrust cover reduced the time for water to pond on the surface (-40%) and commence runoff (-33%), and reduced infiltration (-34%) and sediment production (-68%). Greater biocrust cover had no significant effect on sorptivity or runoff rate/amount, but increased moisture storage (+14%). Infiltration declined most (-56%) at fine scales, and moisture storage was greatest (+36%) at large scales. Effects of biocrust type (cyanobacteria, lichen, moss, mixed), soil texture (sand, loam, clay), and climatic zone (arid, semiarid, dry subhumid) were nuanced. Our synthesis provides novel insights into the magnitude, processes, and contexts of biocrust effects in drylands. This information is critical to improve our capacity to manage dwindling dryland water supplies as Earth becomes hotter and drier.

Ecological water conveyance drives human-water system evolution in the Heihe watershed, China.

Watersheds are coupled with human-water systems where human, and water resources interact and coevolve with each other. Restoration management not only affects the ecosystem itself but also alters the mutual feedback relationship between humans and water, resulting in additional effects and impeding the ecological restoration process. Taking the lower reaches of the Heihe River as an example (Inner Mongolia, PR China), this study investigated the evolution of the human-water system after the implementation of ecological water conveyance using multiple data sources (e.g., remote sensing data, hydrological data, field data and socioeconomic data). We found that (1) after the implementation of ecological water conveyance, vegetation recovered in the last 15 years with an NDVI increasing from 0.10 to 0.13 across the region except some degraded areas near the river; (2) besides restoring the target ecosystem, ecological water conveyance also promoted socioeconomic development and affected the water resources utilization; (3) after 15 years' water conveyance, the coupled human-water system changed from the early ecological water deficit to the present ecological-socioeconomic water-use trade-off with negative impact resulted from agriculture expansion and water usage conflict between the middle and the lower reaches. These effects impeded the restoration of the ecological environment and aggravated the conflicts of water resources utilization within the whole Heihe watershed, consistent with of the hypothesized disturbance effect transmutation. Our results highlighted that analysis on the mutual feedback effect in the coupled human-water system, and dynamic adjustments for restoration measures are needed for sustainable watershed management.

Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease.

Hepatic cystogenesis in polycystic liver disease (PLD) is associated with abnormalities in multiple cellular processes, including elevated cAMP and overexpression of histone deacetylase 6 (HDAC6). Disease progression in polycystic kidney (PCK) rats (an animal model of PLD) is attenuated by inhibition of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in hepatorenal cystogenesis were examined in PCK rats treated with a pan-HDAC inhibitor, panobinostat; three specific HDAC6 inhibitors, ACY-1215, ACY-738, and ACY-241; and a combination of ACY-1215 and the somatostatin receptor analogue, pasireotide. We also assessed effects of ACY-1215 and pasireotide alone and in combination on cell proliferation, cAMP production, and expression of acetylated α-tubulin in vitro in cultured cholangiocytes and the length of primary cilia and the frequency of ciliated cholangiocytes in vivo in PCK rats. Panobinostat and all three HDAC6 inhibitors decreased hepatorenal cystogenesis in PCK rats. ACY-1215 was more effective than other HDAC inhibitors and was chosen for combinational treatment. ACY-1215 + pasireotide combination synergistically reduced cyst growth and increased length of primary cilia in PCK rats. In cultured cystic cholangiocytes, ACY-1215 + pasireotide combination concurrently decreased cell proliferation and inhibited cAMP levels. These data suggest that the combination of drugs that inhibit HDAC6 and cAMP may be an effective therapy for PLD.

Cholangiocyte autophagy contributes to hepatic cystogenesis in polycystic liver disease and represents a potential therapeutic target.

Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment options and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed functional pathway cluster analysis and next-generation sequencing, transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes. A three-dimensional culture model was used to study the effects of molecular and pharmacologic inhibition of autophagy on hepatic cystogenesis in vitro, and the polycystic kidney disease-specific rat, an animal model of PLD, to study the effects of hydroxychloroquine, a drug that interferes with the autophagy pathway, on disease progression in vivo. Assessment of the transcriptome of PLD cholangiocytes followed by functional pathway cluster analysis revealed that the autophagy-lysosomal pathway is one of the most altered pathways in PLD. Direct evaluation of autophagy in PLD cholangiocytes both in vitro and in vivo showed increased number and size of autophagosomes, lysosomes, and autolysosomes; overexpression of autophagy-related proteins (Atg5, Beclin1, Atg7, and LC3); and enhanced autophagic flux associated with activation of the cAMP-protein kinase A-cAMP response element-binding protein signaling pathway. Molecular and pharmacologic intervention in autophagy with ATG7 small interfering RNA, bafilomycin A1 , and hydroxychloroquine reduced proliferation of PLD cholangiocytes in vitro and growth of hepatic cysts in three-dimensional cultures. Hydroxychloroquine also efficiently inhibited hepatic cystogenesis in the polycystic kidney disease-specific rat. CONCLUSION: Autophagy is increased in PLD cholangiocytes, contributes to hepatic cystogenesis, and represents a potential therapeutic target for disease treatment. (Hepatology 2018;67:1088-1108).

Can Patients Trust Online Health Information? A Meta-narrative Systematic Review Addressing the Quality of Health Information on the Internet.

BACKGROUND: The Internet has become a leading source of health information accessed by patients and the general public. It is crucial that this information is reliable and accurate. OBJECTIVES: The purpose of this systematic review was to evaluate the overall quality of online health information targeting patients and the general public. METHODS: The systematic review is based on a pre-established protocol and is reported according to the PRISMA statement. Eleven databases and Internet searches were performed for relevant studies. Descriptive statistics were used to synthesize data. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the methodological quality of the included studies. RESULTS: Out of 3393 references, we included 153 cross-sectional studies evaluating 11,785 websites using 14 quality assessment tools. The quality level varied across scales. Using DISCERN, none of the websites received a category of excellent in quality, 37-79% were rated as good, and the rest were rated as poor quality. Only 18% of websites were HON Code certified. Quality varied by affiliation (governmental was higher than academic, which was higher than other media sources) and by health specialty (likely higher in internal medicine and anesthesiology). CONCLUSION: This comprehensive systematic review demonstrated suboptimal quality of online health information. Therefore, the Internet at the present time does not provide reliable health information for laypersons. The quality of online health information requires significant improvement which should be a mandate for policymakers and private and public organizations.

Woody encroachment: social-ecological impacts and sustainable management.

Woody plants are encroaching across terrestrial ecosystems globally, and this has dramatic effects on how these systems function and the livelihoods of producers who rely on the land to support livestock production. Consequently, the removal of woody plants is promoted widely in the belief that it will reinstate former grasslands or open savanna. Despite this popular management approach to encroachment, we still have a relatively poor understanding of the effects of removal on society, and of alternative management practices that could balance the competing needs of pastoral production, biodiversity conservation and cultural values. This information is essential for maintaining both ecological and societal benefits in encroached systems under predicted future climate changes. In this review, we provide a comprehensive synthesis of the social-ecological perspectives of woody encroachment based on recent studies and global meta-analyses by assessing the ecological impacts of encroachment and its effects on sustainable development goals (SDGs) when woody plants are retained and when they are removed. We propose a working definition of woody encroachment based on species- and community-level characteristics; such a definition is needed to evaluate accurately the effects of encroachment. We show that encroachment is a natural process of succession rather than a sign of degradation, with encroachment resulting in an overall 8% increase in ecosystem multifunctionality. Removing woody plants can increase herbaceous plant richness, biomass and cover, but at the expense of biocrust cover. The effectiveness of woody plant removal depends on plant identity, and where, when and how they are removed. Under current management practices, either removal or retention of woody plants can induce trade-offs among ecosystem services, with no management practice maximising all SDGs [e.g. SDG2 (end hunger), SDG13 (climate change), SDG 15 (combat desertification)]. Given that encroachment of woody plants is likely to increase under future predicted hotter and drier climates, alternative management options such as carbon farming and ecotourism could be effective land uses for areas affected by encroachment.

Cardiovascular protection of YiyiFuzi powder and the potential mechanisms through modulating mitochondria-endoplasmic reticulum interactions.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and represent a major public health challenge. YiyiFuzi Powder (YYFZ), composed of Coicis semen and Fuzi, is a classical traditional Chinese medicine prescription from the Synopsis of Golden Chamber dating back to the Han Dynasty. Historically, YYFZ has been used to treat various CVD, rooted in Chinese therapeutic principles. Network pharmacology analysis indicated that YYFZ may exhibit direct or indirect effects on mitochondria-endoplasmic reticulum (ER) interactions. This review, focusing on the cardiovascular protective effects of Coicis semen and Fuzi, summarizes the potential mechanisms by which YYFZ acts on mitochondria and the ER. The underlying mechanisms are associated with regulating cardiovascular risk factors (such as blood lipids and glucose), impacting mitochondrial structure and function, modulating ER stress, inhibiting oxidative stress, suppressing inflammatory responses, regulating cellular apoptosis, and maintaining calcium ion balance. The involved pathways include, but were not limited to, upregulating the IGF-1/PI3K/AKT, cAMP/PKA, eNOS/NO/cGMP/SIRT1, SIRT1/PGC-1α, Klotho/SIRT1, OXPHOS/ATP, PPARα/PGC-1α/SIRT3, AMPK/JNK, PTEN/PI3K/AKT, ß2-AR/PI3K/AKT, and modified Q cycle signaling pathways. Meanwhile, the MCU, NF-κB, and JAK/STAT signaling pathways were downregulated. The PERK/eIF2α/ATF4/CHOP, PERK/SREBP-1c/FAS, IRE1, PINK1-dependent mitophagy, and AMPK/mTOR signaling pathways were bidirectionally regulated. High-quality experimental studies are needed to further elucidate the underlying mechanisms of YYFZ in CVD treatment.

Erratum: DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites.

[This corrects the article DOI: 10.1016/j.isci.2023.106444.].

Compound hot-dry events greatly prolong the recovery time of dryland ecosystems.

Compound hot-dry events cause more severe impacts on terrestrial ecosystems than dry events, while the differences in recovery time (ΔRT) between hot-dry and dry events and their contributing factors remain unclear. Both remote sensing observations and eddy covariance measurements reveal that hot-dry events prolong the recovery time compared with dry events, with greater prolongation of recovery time in drylands than in humid regions. Random forest regression modeling demonstrates that the difference in vapor pressure deficit between hot-dry and dry events, with an importance score of 35%, is the major factor contributing to ΔRT. The severity of stomatal restriction exceeds that of non-stomatal limitation, which restricts the vegetation productivity that is necessary for the recovery process. These results emphasize the negative effect of vapor pressure deficit on vegetation recovery during hot-dry events and project an extension of drought recovery time considering elevated vapor pressure deficit in a warming world.