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N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.

Climate and human activities change spatial and temporal distribution of water and land use. The Tarim River, the largest inland river in China, faced a long-term exploitation of land and water over a rapid economic development. We analyzed land and water use from 1997 to 2019 in Tarim River Basin by Landsat images, and data on hydrology, climate, population, economy and PM2.5 (air particulate matter ≤2.5 μm). Agricultural land expanded the fastest (4–11%), followed by natural vegetation (15–16%) and water area (4–5%) with population and economic increase. Air quality (PM2.5 μg m−3) improved in upper (62–27) and middle (48–17) reaches. The water area in lower increase 5% because of ecological water delivery since 2000. Land use in the lower reach was dominated by agriculture, where the downstream runoff consumption increased by 6.8 times. The average annual air temperature and precipitation gradually increased by 0.5 °C and 51 mm in source and 0.9 °C and 30 mm in main reaches. The average annual water consumption in upper and middle reaches was 4 × 109 m3, accounting for 87% of input runoff in the main reach. Water consumption in middle reach increased by 33 times in 2009–2017. The industry structure was changing from primary to secondary and tertiary industry. To sum up, implementation of water saving strategies and ecological water delivery restored local ecology. Sustainable strategies should be applied facing industrialization. Furthermore, changing the industry structure and restoring the degraded farmlands to grasslands or forests would keep sustainability of Tarim River Basin.

Objective: To investigate the protective effect of Tadehaginoside on vascular endothelial cell injury induced by reactive nitrogen. Methods: MTT colorimetry was used to detect the effect of Tadehaginoside on the survival rate of EA.hy 926 endothelial cells in the concentration range of 5～160 μmol/L; 1 h after pre-administration of Tadehaginoside, 0.5 mM GSNO was given to damage endothelial cells. Detect the mitochondrial specific factors COX-1, ND-1 and inflammatory factor IL-1β of EA.hy 926 cells damaged by GSNO by Real time-PCR method gene intervention. At the same time, Western blot was used to detect the changes in Bax and Bcl-2 protein expression. The mitochondrial membrane potential kit (JC-1) was used to detect the change of Tadehaginoside on the mitochondrial membrane potential after GSNO induced EA.hy 926 cell injury. Results: The results of the MTT method showed that Tadehaginoside had no obvious cytotoxicity on EA.hy 926 cells in the range of 5～160 μmol/L, and the optimal protective concentration of the drug was 40 μmol/L. Western Blot method showed that BAX protein expression increased in a time-dependent manner after GSNO damaged EA.hy 926 cells over time, while Bcl-2 protein expression was the opposite. Real time-PCR results showed that Tadehaginoside can significantly up-regulate COX-1 gene (P < 0.05), and can significantly inhibit GSNO induced ND-1 (P < 0.05) and IL-1β gene up-regulation (P < 0.01). At the same time, the results of JC-1 showed that Tadehaginoside could significantly protect the mitochondrial membrane potential from GSNO damage. Conclusion: The GSNO damage model may induce the increase of Bax and other pro-apoptotic proteins through mitochondrial DNA damage and reduce the expression of anti-apoptotic factor Bcl-2. Tadehaginoside has a certain protective effect on endothelial cell mitochondrial damage induced by reactive nitrogen, and its mechanism is related to inhibiting the expression of ND-1 and IL-1β genes and upregulating the expression of COX-1 genes.

NIR-activated therapies based on light-responsive drug delivery systems are emerging as a remote-controlled method for cancer precise therapy. In this work, fluorescent dye indocyanine green (ICG)-conjugated and bioactive compound gambogic acid (GA)-loaded polymeric micelles (GA@PEG-TK-ICG PMs) were smoothly fabricated via the self-assembly of the reactive oxygen species (ROS)-responsive thioketal (TK)-linked amphiphilic polymer poly(ethyleneglycol)-thioketal-(indocyanine green) (PEG-TK-ICG). The resultant micelles demonstrated increased resistance to photobleaching, enhanced photothermal conversion efficiency, NIR-controlled drug release behavior, preferable biocompatibility, and excellent tumor accumulation performance. Moreover, upon an 808 nm laser irradiation, the micellar photoactive chromophore ICG converted the absorbed optical energy to both hyperthermia for photothermal therapy (PTT) and ROS as the feedback trigger to the micelles for the tumor-specific release of GA, which could serve as not only a chemotherapeutic drug to directly kill tumor cells but also a heat shock protein 90 (HSP90) inhibitor to realize the photothermal sensitization. As a result, an extremely high tumor inhibition rate (97.9%) of mouse 4 T1 breast cancer models was achieved with negligible side effects after the chemo-photothermal synergistic therapy. This NIR-activated nanosystem with photothermal self-sensitization function may provide a feasible option for the effective treatment of aggressive breast cancers.

Interpreting the similarities and dissimilarities in spatiotemporal variations and various controls between surface and canopy urban heat islands (UHIs) is critical for a better understanding of their vertical structure. Preceding comparisons of the surface UHI (SUHI) and canopy UHI (CUHI), however, remain mostly restricted either in a single city or over a few cities within limited background climates; therefore, the associated similarities and dissimilarities between the SUHI and CUHI under different climates, especially at a global scale, remain largely unknown. Based on both satellite and in situ data, we simultaneously investigated the spatiotemporal patterns of the SUHI intensity (SUHII) and CUHI intensity (SUHII) of 366 global cities within various background climates. We further investigated the different impacts of several controls (e.g., vegetation coverage, population size, precipitation) on SUHII and CUHII. Our results indicate the following: (1) For the selected 366 cities, the annual mean SUHII is higher than CUHII by 1.1 ± 1.9 °C (mean ± Std) during the day and 0.3 ± 1.5 °C (mean ± Std) at night. The SUHII and CUHII in the equatorial, warm temperate, and snow climates are generally consistent with the above characteristics (i.e., SUHII > CUHII), however, in arid regions SUHII is lower than CUHII by 0.8 °C during the day. (2) The annual mean day–night difference in SUHII is positive (i.e., 0.6 ± 1.8 °C (mean ± Std)), while the difference in CUHII becomes negative (i.e., −0.2 ± 1.6 °C (mean ± Std)), indicating that urbanization increases the diurnal temperature range (DTR) based on land surface temperature, but it decreases the DTR based on surface air temperature. (3) Despite the high correlation between vegetation coverage and impervious surface percentage (ISP), their impacts on SUHII and CUHII were not consistent. The urban–rural difference in ISP exerts an insignificant impact on both SUHII and CUHII during the day and a greater impact on CUHII than on SUHII at night, whereas the urban–rural difference in vegetation coverage has a greater impact on SUHII than on CUHII during the day, while the opposite occurs at night. The impacts of population size on SUHII and CUHII are much greater during the night than on the day in which their impacts can be minimal. The relationship between annual mean precipitation and SUHII is positive during the day but negative at night, while for CUHII, their relationship is insignificantly negative both during the day and at night. These results can improve our understanding of the spatiotemporal patterns and controls of these two types of UHIs under various climates.

The two-step strategy screening based high throughput calculation is an effective method to search for highly active single atom catalysts (SACs) for efficient nitrogen reduction reaction (NRR), sharing a common feature of active metal centers MN4. However, this method faces the lack of descriptor for designing SACs due to limited data. Herein we proposed a robust empirical rule to estimate 312 credible limiting potentials for NRR over 104 C3N-supported SACs. It is found that the limiting potential scales clearly with the adsorption free energies of two key reaction intermediates (∗N2H and ∗NH2), which are significantly dependent on the structure relating descriptor φ, and the activity of SACs with and without N coordination exhibits similar catalytic efficiency. We identified four high-performance SACs having moieties of CrC2N2, CrC4, MnC4 and OsC4 with high selectivity towards NRR and competitive limiting potentials of −0.40, −0.45, −0.53 and −0.54 V, respectively. The φ values for these four SACs are around 19–25 which fall within its optimal ranges of 20–25 validating its prediction fidelity. This work broadens the discovery of two-dimensional carbon-nitrides supported SACs free of N coordination towards efficient N2 reduction and opens a new route of descriptor-guided design of efficient SACs for electrocatalysis process.

Social memory between the same gender or even different gender is a complex and heavily modulated process in the nervous system. It is important for an individual to form social memory between the opposite sex to either increase mating opportunities with multiple partners or form monogamous pair bonding. Therefore, a specific neuronal circuit to regulate social sexual memory may enhance the mating opportunity for an individual. It has been shown that both the auditory and somatosensory systems could increase the activity of oxytocin neurons in the paraventricular nucleus to regulate social behaviors. Although light exposure could influence various forms of memory, such as fear and object memory, how luminance signals modulate social recognition memory remains unclear. Here, we show that acute light exposure could impair the socio-sexual recognition memory (SSRM) in male mice. Contrary to sound and touch, light stimulation could inhibit oxytocin neurons in the SON (SONOT) through M1 SON-projecting ipRGCs and GABAergic neurons in the peri-SON (pSONGABA). Optogenetic activation of SONOTneurons with channelrhodopsin is sufficient to enhance the SSRM performance in male mice, even under light conditions. Our results show that the visual system could modulate SSRM through a succinct ipRGCs-pSONGABA-SONOT neuronal circuitry. Together, we demonstrate a dedicated neuronal circuit of how luminance affects memory formation for an individual toward different sex through the oxytocin system, a powerful modulatory neurohormone in the central nervous system.

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKi) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiates the pro-apoptotic effects of MAPKi via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Co-targeting PEX3 and UGCG selectively eliminates a subset of metabolically active, drug-tolerant CD36+melanoma persister cells, thereby sensitizing melanoma to MAPKi and delaying resistance. Increased levels of peroxisomal genes andUGCGare found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restores MAPKi sensitivity in multiple models of therapy resistance. Finally, triple therapy comprised of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor and a MAPKi demonstrates potent anti-tumor activity in pre-clinical melanoma models, thus representing a promising approach for melanoma treatment.HighlightsInhibiting peroxisome biogenesis uncovers a metabolic vulnerability in melanomaCD36+persister melanoma cells tolerate MAPK-targeted therapy through peroxisome/UGCG mediated metabolic rewiringDual blockade of PEX3 and UGCG potentiates melanoma response to MAPK-targeted therapies and restores therapeutic sensitivity in MAPKi-resistant tumorsNNC 55-0396 is a PEX3-PEX19 binding inhibitor with potent anti-tumor activity in melanoma

Dengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated.To investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology.A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds.In MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3-O-glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment.DZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis.

The removal of impurity gases (N

Purpose c-Type cytochromes are essential for extracellular electron transfer (EET) in electroactive microorganisms. The expression of appropriate c-type cytochromes is an important feature of these microorganisms in response to different extracellular electron acceptors. However, how these diverse c-type cytochromes are tightly regulated is still poorly understood. Methods In this study, we identified the high co-fitness genes that potentially work with different c-type cytochromes by using genome-wide co-fitness analysis. We also constructed and studied the co-fitness networks that composed of c-type cytochromes and the top 20 high co-fitness genes of them. Results We found that high co-fitness genes of c-type cytochromes were enriched in signal transduction processes in Shewanella oneidensis MR-1 cells. We then checked the top 20 co-fitness proteins for each of the 41 c-type cytochromes and identified the corresponding signal proteins for different c-type cytochromes. In particular, through the analysis of the high co-fitness signal protein for CymA, we further confirmed the cooperation between signal proteins and c-type cytochromes and identified a novel signal protein that is putatively involved in the regulation of CymA. In addition, we showed that these signal proteins form two signal transduction modules. Conclusion Taken together, these findings provide novel insights into the coordinated utilization of different c-type cytochromes under diverse conditions.

The accumulation of soluble β-amyloid aggregates (sAβs) is one of the main culprits in Alzheimer’s disease (AD) progression, which can lead to synaptic dysfunction and subsequent neurodegeneration....

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2–eIF4E axis promotes translation of prometastatic mRNAs in tumor cells, but its role in modulating the function of nontumor cells in the PPBC microenvironment has not been explored. Here, we used a combination of in vivo PPBC models and in vitro assays to study the effects of inactivation of the MNK1/2–eIF4E axis on the protumor function of select cells of the tumor microenvironment. PPBC mice deficient for phospho-eIF4E (eIF4ES209A) were protected against lung metastasis and exhibited differences in the tumor and lung immune microenvironment compared with wild-type mice. Moreover, the expression of fibroblast-derived IL33, an alarmin known to induce invasion, was repressed upon MNK1/2–eIF4E axis inhibition. Imaging mass cytometry on PPBC and non-PPBC patient samples indicated that human PPBC contains phospho-eIF4E high–expressing tumor cells and CD8+ T cells displaying markers of an activated dysfunctional phenotype. Finally, inhibition of MNK1/2 combined with anti–PD-1 therapy blocked lung metastasis of PPBC. These findings implicate the involvement of the MNK1/2–eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. Significance: This study investigates the MNK1/2–eIF4E signaling axis in tumor and stromal cells in metastatic breast cancer and reveals that MNK1/2 inhibition suppresses metastasis and sensitizes tumors to anti–PD-1 immunotherapy.

Estimating future temporal patterns of Surface Urban Heat Islands (SUHIs) on multiple time scales is an ongoing research endeavor. Among these time scales, estimation of next-day SUHIs is of special significance to urban residents, yet we currently lack a simple but efficient approach for making such estimations. In the present study, we propose a statistical strategy for estimating next-day nighttime SUHIs, based on incorporating various SUHI controls into a support vector machine regression (SVR) model. The majority of both the surface controls (including factors related to land cover and solar radiation) and meteorological controls (including temperature fluctuations, relative humidity, accumulated precipitation, wind speed, aerosol optical depth, and soil moisture) that have previously been found to account for daily SUHI variations were used as estimators, and we provide estimations for both the overall SUHI intensity (SUHII) and pixel-by-pixel Gaussian-based LSTs over 59 Chinese megacities. For the overall SUHII, the mean absolute error (MAE) is 0.67 K on average, and the mean absolute percentage error (MAPE) is no more than 25% for more than 90% of the cities. For the pixel-by-pixel LSTs, the associated MAE is less than 2.0 K in most scenarios. In addition, the contribution from each selected estimator to SUHII estimation is assessed comprehensively. Among all the estimators, the contribution from relative humidity is the greatest, followed by rural surface temperature and surface air temperature. Moreover, for nearly 78% of the cities, the estimators related to day-to-day SUHI variations make a larger contribution than those related to intra-annual SUHI variations. We conclude that our simple yet effective statistical approach for estimating next-day SUHIs can potentially help urban residents to better adapt to urban heat stress.

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans‐Leuk1 epithelial cell co‐culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking‐induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans.

Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson’s disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality.

Amyloid β peptide (Aβ) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Currently, decreasing Aβ production and preventing Aβ aggregation are thought to be important strategies in anti-AD therapy. However, inhibiting Aβ production or aggregation in isolation is not sufficient to reverse the neurodegenerative process of AD patients in clinical testing. Here, a self-assembly molecular chaperone (SAMC) consisting of γ-secretase inhibitor DAPT and mixed-shell polymeric micelles is devised, serving as a bifunctional suppressor of AD. This two-in-one combinational system can simultaneously inhibit Aβ production and aggregation, which would contribute to enhancing the therapeutic effect by decreasing Aβ levels. Decorating a neuron-specific RVG29 peptide onto the surface, the DAPT-incorporated SAMC can specifically target neuronal cells and, thus, will relieve the strong side effect of DAPT on normal cells. Therefore, this combination strategy holds great potential to open up an avenue for AD treatment.

Protein therapeutics have been viewed as powerful candidates for cancer treatment by virtue of highly specific bioactivity and minimized adverse effects. However, the intracellular delivery of protein drugs remains enormously challenging due to multiple successive biological barriers

Pogostemon cablin has been indicated to treat many kinds of diseases and the progression of cancers, such as colorectal cancer. However, the effects of P. cablin extract (PPa extract) against acute myeloid leukemia have not been investigated. Thus, this study explored the anticancer potential of PPa extract and its mechanism in HL‐60 cells. The MTT assay results showed that PPa extract significantly inhibited the proliferation of HL‐60 cells in a dose‐dependent manner and affected cell morphology, causing cell shrinkage and the formation of debris. PPa extract blocked cell cycle progression at the G0/G1 phase in a dose‐ and time‐dependent manner and induced cell apoptosis, as shown by the observation of DNA fragments and apoptotic bodies. Furthermore, PPa extract caused the accumulation of a population of cells at G0/G1 phase via a reduction in p‐Rb, increasing p21 expression, and downregulating cell cycle regulator protein expression. Then, PPa extract was found to activate the extrinsic and intrinsic apoptosis pathways, leading to cell death. These data demonstrated that PPa extract exerted inhibitory activity and triggered cell apoptosis in HL‐60 cells and that PPa extract might be a chemopreventive agent for cancer therapy., Pogostemon cablin extract contained potential anticancer compound to suppress HL‐60 cell growth by blocking cell cycle progression and inducing cell apoptosis.

The ever-increasing space exploration enterprise calls for novel and high-quality radiation-resistant materials, among which nonlinear optical materials and devices are particularly scarce. Two-dimensional (2D) materials have shown promising potential, but the radiation effects on their nonlinear optical properties remain largely elusive. We previously fabricated 2D bismuthene for mode-locking sub-ns laser; herein, their space adaption was evaluated under a simulated space radiation environment. The as-synthesized thin layers of bismuthene exhibited strong third-order nonlinear optical responses extending into the near-infrared region. Remarkably, when exposed to 60Co γ-rays and electron irradiation, the bismuthene showed only slight degradation in saturable absorption behaviors that were critical for mode-locking in space. Ultrafast spectroscopy was applied to address the radiation effects and damage mechanisms that are difficult to understand by routine techniques. This work offers a new bottom-up approach for preparing 2D bismuthene, and the elucidation of its fundamental excited-state dynamics after radiation also provides a guideline to optimize the material for eventual space applications.

Recessions and subsequent recoveries are frequently classified as ‘L‐shaped’ or ‘U‐shaped’, with output losses in the former being permanent and losses in the latter at least partially made up by higher than average growth during the recovery. We estimate the probability of a U‐shaped recovery for postwar NBER recessions. Most earlier recessions were U‐shaped but more recent recessions have been L‐shaped. The shape of recoveries is tracked relatively well by durable consumption, investment, labour hours and employment. Posterior probabilities for the shape of recoveries for nondurable consumption and participation rate are less decisive. However, total factor productivity appears to recover rapidly after all recessions.