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Importance Both the morbidity and mortality of prostate cancer are increasing worldwide. Updated evaluations of prostate cancer burden and its global, regional and national patterns are essential for formulating effective preventive strategies. Objective To investigate prostate cancer incidence, mortality, and disability-adjusted life years (DALYs) between 1990 and 2019 to facilitate preventive measures and control planning. Methods Annual incident cases, deaths, DALYs, age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs rates (ASDRs) of prostate cancer between 1990 and 2019 were derived from the Global Burden of Diseases study 2019. Percentage changes in incident cases, deaths and DALYs and estimated annual percentage changes (EAPCs) in ASIRs, ASMRs and ASDRs were calculated to quantify temporal trends. Correlations between EAPCs and socio-demographic index (SDI) and universal health coverage index (UHCI) were evaluated by Pearson correlation analyses. Results Globally, the number of incident cases, deaths, and DALYs of prostate cancer increased by 116.11%, 108.94%, and 98.25% from 1990 to 2019, respectively. The ASIR increased by an average of 0.26% (95% CI: 0.14%, 0.37%) per year between 1990 and 2019, while the ASMR and ASDR decreased by an average of – 0.75% (95% CI: – 0.84%, – 0.67%) and – 0.71% (95% CI: – 0.78%, – 0.63%) per year in this period, respectively. Epidemic trends in the burdens of prostate cancer were not uniform throughout different groups of SDI or geography. The burdens of prostate cancer varied across SDI regions, with an increasing trend in ASIR, ASMR, and ASDR in low and low-middle SDI regions between 1990 and 2019. A significant positive correlation between the EAPC in ASIR and UHCI was observed in countries with a UHCI Interpretation Prostate cancer remains a major global health burden due to the increase in incident cases, deaths, and DALYs in the past three decades. These increases are likely to continue as the population ages, which indicates a potential talent gap in the trained healthcare workforce. The diversity of prostate cancer development models implies the importance of specific local strategies tailored for each country’s risk factor profile. Prevention, early detection and more effective treatment strategies for prostate cancer are essential.

BackgroundEssential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade.MethodsWe searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution.ResultsOverall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015–2019 [28.1%, 95% confidence interval (CI): 26.4–29.9%] was similar to that in 2009–2014 (29.4%, 95% CI: 27.5–31.3%); lower in the Western region (19.8%, 95% CI: 18.1–21.5%) than Eastern (33.8%, 95% CI: 31.6–36.1%) and Central region (34.5%, 95% CI: 30.6–38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups.ConclusionThe availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

Recessions are associated with sharp increases in turbulence that reshuffles firms' productivity rankings. To study the business cycle implications of turbulence shocks, we use Compustat data to construct a measure of turbulence based on the (inverse of) Spearman correlations of firms' productivity rankings between adjacent years. We document evidence that turbulence rises in recessions, reallocating labor and capital from high-to low-productivity firms and reducing aggregate TFP and the stock market value of firms. A real business cycle model with heterogeneous firms and financial frictions can generate the observed macroeconomic and reallocation effects of turbulence. In the model, increased turbulence makes high-productivity firms less likely to remain productive, reducing their expected equity values and tightening their borrowing constraints relative to low-productivity firms. Thus, labor and capital are reallocated to low-productivity firms, reducing aggregate TFP and generating a recession with synchronized declines in aggregate output, consumption, investment, and labor hours, in line with empirical evidence.

Totally laparoscopic right colectomy has been demonstrated to be safe and feasible. Two manners of anastomosis, namely, antiperistaltic and isoperistaltic stapled side-to-side anastomosis, have been described before. However, research concerning the influence of different peristaltic orientations on anastomosis is rare and, if there is, included relatively small cases without long-term outcomes. The aim of this study was to compare the short- and long-term outcomes of intracorporeal isoperistaltic side-to-side anastomosis and antiperistaltic side-to-side anastomosis for right colectomy.We retrospectively reviewed 214 consecutive patients who underwent totally laparoscopic right colectomy from January 2017 to December 2020 at our medical center. Two modalities of anastomosis were used: isoperistaltic totally side-to-side anastomosis and antiperistaltic totally side-to-side anastomosis. Data on demographics, disease features, pathological characteristics, operative details, and short-term outcomes were collected and analyzed.We found that operative features such as operating time, intraoperative bleeding, length of resected intestine, number of harvested lymph nodes, and length of incision, as well as measures of postoperative recovery such as time to first flatus, time to first defecation, and length of stay, were statistically comparable between the 2 groups. The postoperative complication rate was also similar between the 2 groups. The median follow-up time was 35.6 months, and no differences were observed in the long-term outcomes.Intracorporeal isoperistaltic side-to-side anastomosis can achieve short- and long-term outcomes similar to those of antiperistaltic side-to-side anastomosis. Both techniques are safe and feasible.

Two crystalline silver alkynyl assemblies, namely, [Ag6(tBuC≡C)4 L1]n (1), [Ag10(tBuC≡C)6(L2)2]n (2) (H2L1 = 1,8-naphthalene dicarboxylic acid and H2L2 = 1,4-naphthalene dicarboxylic acid) have been obtained by the reaction of polymeric [tBuC≡CAg]n with silver salts and dicarboxylic acids under mild solvothermal conditions. Compounds 1 and 2 are coordination polymers of irregular silver alkynyl clusters. 1 is chains of cube-like silver clusters connected with L1 and tBuC≡C- ligands. In compound 2, the Ag10 clusters surrounded by six tBuC≡C- ligands are linked by silver atoms to 1D chains, which are further extended by L2 ligands to a rare 3D framework. From the topological view, the structure of 2 can be regarded as α-Po topology. The luminescence properties indicated that the two complexes display more than one peak maxima at 298 K using 335 nm excitation.

Background: With the increasing need to explore the association between interpregnancy interval (IPI) and adverse maternal and neonatal outcome, numerous studies have been conducted worldwide. However, national reports of the IPI in China are lacking. Furthermore, except for age as a known factor for IPI and adverse maternal and neonatal outcomes, the effect of gestational age in previous pregnancy is unknown. The aim of this study was to determine the IPI distribution between 2010 and 2019 and identify the effect of IPI and gestational age in previous pregnancy on adverse maternal and neonatal outcomes in China. Methods: We used individual data from China's National Maternal Near Miss Surveillance System (NMNMSS) between 2010 and 2019. The surveillance system collected data prospectively on all pregnant and postpartum women admitted to the obstetric department. The analysis was restricted to women with records of at least two consecutive singleton births and without any complication that the NMNMSS collected during their previous pregnancy. Multivariable generalized linear models with the restricted cubic spline (RCS) were used to evaluate the effect of IPI on each adverse neonatal and maternal outcome on different categories of gestational age in previous pregnancy. Further analysis was performed in subgroups categorized by the gestational age of previous pregnancy. Results: Over the study period, 408,843 women with 420,810 pregnancies were enrolled in our study. The median and quartile range of IPI was 32 [22, 47] months. Few women (49,084, 11.67%) became pregnant again within an extremely short (≤6 months) or long (≥60 months) IPI, and over half (289,846, 68.88%) of the women became pregnant again after an IPI between 7 and 42 months. The risk of large for gestational age (LGA), Gestational Diabetes Mellitus (GDM) and gestational hypertension was increased with increased IPI, while the risk of spontaneous preterm and small for gestational age (SGA) was inversely decreased with increased IPI. The relationship between IPI and all the other adverse neonatal and maternal outcomes was in a “U” shape. The risk of adverse neonatal and maternal outcomes differs between subgroups stratified by gestational age in the previous pregnancy. The risk of spontaneous preterm and abortion at short IPI, iatrogenic preterm, GDM, preeclampsia or eclampsia and gestational hypertension at long IPI increased more when women were of a greater gestational age in the previous pregnancy. Conclusions: This was the first comprehensive exploration of the IPIs of Chinese women from a national database. In this research, both extreme short and long IPI were associated with a higher risk of adverse maternal and neonatal outcomes. The gestational age in the previous pregnancy was also a determinant factor for the adverse maternal and neonatal outcomes in subsequent pregnancies. Funding Statement: This study was supported by the National Key R&D Program of China (Grant No. 2019YFC1005100), the National Health Commission of the People’s Republic of China, the China Medical Board (Grant No. 11-065), the WHO (Grant No. CHN-12-MCN-004888), and UNICEF (Grant No. 2016EJH016). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committee of the West China Second University Hospital.

We present evidence that monetary policy easing reduces bank risk-taking but exacerbates capital misallocation in China after implementing the Basel III capital regulationsin2013. Thenewregulationstightenedbankcapitalrequirementsandintroduced a new risk-weighting approach to calculating the capital adequacy ratio (CAR). To meet tightened capital requirements, a bank can boost its effective CAR by raising capital or by increasing the share of lending to low-risk borrowers. Using confidential loan-level data from a large Chinese commercial bank, merged with firm-level data on a large set of manufacturing firms, we document robust evidence that a monetary policy expansion raises the share of new bank loans to state-owned enterprises (SOEs) after 2013, but not before, because SOE loans receive high credit ratings under government guarantees. Since SOEs are on average less productive than private firms, shifts in bank lending toward SOEs exacerbate capital misallocations, reducing aggregate productivity. We construct a two-sector general equilibrium model with bank portfolio choices and show that, under calibrated parameters, an expansionary monetary policy shock raises the share of bank lending to SOEs, leading to persistent declines in total factor productivity that partially offset the expansionary effects of monetary policy.

Preparing activated carbon with high volumetric performance in organic electrolyte is crucial for developing high-energy and miniaturized supercapacitors, but still challenging because high surface area and large pore size are required to effectively store large-sized organic electrolyte ions, which usually result in the low density. Herein, an ultrafast strategy is proposed to tailor the interconnected porous structure of activated carbon through introducing CO2 at the end of homogeneous activation. The uniformly distributed potassium components in carbon matrix promote a robust catalytic etching by CO2, leading to precise tailoring of the ultramicropores (0.50-0.72 nm) to large micropores (0.81-1.14 nm) within only two minutes. The optimized sample with both high surface area and compaction density (2147 m2 g-1, 0.68 g cm-3) shows high gravimetric and volumetric capacitances (155 F g-1 and 106 F cm-3 at 1 A g-1) as well as good rate performance (102 F g-1 and 70 F cm-3 at 20 A g-1) in organic electrolyte. The symmetric supercapacitor achieves high energy densities of 35 Wh kg-1 and 24 Wh L-1 at 573 W kg-1 and 395 W L-1, respectively, indicating great potential of the ultrafast tailoring strategy for practical application.

Objective: Stage II colorectal cancer (CRC) manifests various treatment responses and outcomes. To assess the recurrence risk, we established a molecular subtype classification for stage II CRC. Methods: We developed a novel molecular subtyping clustering algorithm CRC-MSC for determining molecular subtypes in stage II CRC using only whole exome sequencing (WES). It utilized a specified distance estimate, calculated according to the shared alterations among samples. CRC-MSC was qualified for classification and risk stratification on samples from National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA). To facilitate application to individual management decision, this algorithm was simplified by a decision tree classifier (CRC-MDTC). Phylogenetic analysis was conducted to clarify the mutated genes constituting the decision tree. Results: Using CRC-MSC successfully subtyped 60 stage II CRC samples from NCC into three groups, favorable prognosis (S-I), unfavorable prognosis (S-II) and intermediate (S-III) groups, which was verified in TCGA dataset. These subtypes feature unique molecular, clinicopathological phenotypes and clinical outcomes, especially immune traits.A simplified version of decision tree classifier (CRC-MDTC), TMB, PRKDA and KRAS alterations are three top classification indications, could also reliably categorize samples into three groups. It was validated in an independent cohort with an accuracy of 74.7%. CRC-MSC and CRC-MDTC were available at https://bioinfo.org/crcmsc. Conclusions: In addition to the initial risk evaluation, we developed a framework for the classification of stage II CRC subtypes based on genome profiling, which may shed new light on the management of patients with stage II CRC, especially with regarded to individualized chemotherapy and immunotherapy. Funding: This work was supported by National Program Project for Precision Medicine in National Research and Development Plan of China (2016YFC0905300), and CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-2-002). Declaration of Interest: None to declare. Ethical Approval: The ethical approval of this study was granted by the Institutional Review Board of Chinese Academy of Medical Sciences (CHCAMS, Beijing, China)/National Cancer Center (NCC, Beijing, China).

Bio-inspired mimicking natural structures generally duplicate the three dimensional “hard brick-and-soft mortar” structure that may overcome the intrinsic brittleness of the brick, resulting in an improved mechanical performance. Here we for the first time propose an anti-bioinspired strategy of designing metallic composite with a soft brick (commercially pure titanium (CP-Ti)) confined by hard mortars (Ti6Al4V alloy), where the three dimensional minority of hard mortar (with a volume fraction of ~14%) was fabricated by using selective laser melting (SLM), and the bricks were introduced by filling in CP-Ti powders followed by the hot isostatic pressing (HIP). The resultant nacre-like structured composite exhibits a periodic distribution of “soft-brick” and “hard-mortar” domains with a remarkable interface between them. This unique structure leads to a combination of high strength and high fracture toughness that both exceed the respective value calculated using the rule of mixtures (ROM). Three dimensional heterogeneous plastic deformation between the two domains induces the mechanical incompatibility, which has been confirmed by the presence of higher density of geometrically necessary dislocations (GNDs) in front of the interface. The large amount of GNDs was believed primarily responsible for the extraordinary strengthening and toughening beyond the ROM. This novel strategy of artificial designing three dimensional “soft brick and hard mortar” structure could be further extended to other metals and alloys, shedding lights on developing new type of heterogeneous materials applicable to industry.

Background: Frontline epidemic prevention workers play a pivotal role against COVID-19. Their baseline of dietary and behavior habits and willingness to change these habits after experiencing the outbreak of COVID-19 remains unclear. Methods: A self-developed online questionnaire survey was carried out via the WeChat platform, and 22,459 participated, including 9402 frontline epidemic prevention workers. Findings: Before COVID-19, 23.9% of frontline epidemic prevention workers reported a high-salt diet, 46.9% reported a high frequency of fried food intake, 21.6% reported a low frequency of fresh vegetable intake, and 50.9% smoked cigarettes. After experiencing the outbreak of COVID-19, 34.6% had the willingness to reduce salt intake, and 43.7% want to reduce the frequency of pickled vegetable intake. 37.9% had the willingness to decrease or quit smoking, and 44.5% want to increase sleep duration. Significant differences in the baseline of dietary and behavioral habits and willingness to change their habits were observed between the frontline epidemic prevention worker and others(P

Both stable Th2Zn17-type and metastable TbCu7-type phases of anisotropic Nd-Fe ultrafine particles are prepared selectively by controlling the cooling rate using the low-oxygen induction thermal plasma (LO-ITP) process. The cooling rate is controlled by introducing the additional Ar gas at the end of the plasma flame. Moreover, numerical calculations based on a binary aerosol formation-growth model clarifies the alloying mechanism during rapid cooling wherein Nd-Fe vapor solidifies. The metastable Nd-Fe alloy ultrafine particle is formed in the cooling rate of 5 × 105 K/sec via the alloy droplet which is formed after the Fe and Nd vapors convert simultaneously into the liquid phase. The mean particle sizes of obtained ultrafine alloy powders without and with quenching are 76.3 ± 24.2 nm and 37.0 ± 12.5 nm, respectively. Electron microscopy observation reveals that the obtained particles are single crystalline. The Nd concentration of Nd-Fe particles shows a distribution in the range of 10.1–12.6 at%. X-ray diffraction and magnetic measurement demonstrate that the obtained particles are anisotropic and can be aligned by external magnetic field. Therefore, this process paves the way to achieve a new-generation anisotropic permanent magnet.

Background: Since December 2019, COVID-19 has emerged in Wuhan, China and spread rapidly throughout China So far, there is still no explicit therapeutic regime

Background: The outbreak of COVID-19 has laid unprecedented threats and challenges to health workers (HWs) in Wuhan, China. We aimed to assess the sociodemographic characteristics and hospital support measures associated with the immediate psychological impact on HWs at Tongji Hospital in Wuhan during COVID-19 outbreak. Methods: We conducted a single-center, cross-sectional survey of HWs via online questionnaires between February 8th and 10th, 2020. We evaluated stress, depression and anxiety by IES-R, PHQ-9, and GAD-7, respectively. We also designed a questionnaire to assess the perceptions of threat of COVID-19, and the effect of the hospital’s support measures. Multivariate logistic regression was used to identify predictors of acute stress, depression, and anxiety. Findings: We received 5062 completed questionnaires (response rate, 77.1%). 29.8%, 13.5% and 4.1% HWs reported stress, depression and anxiety symptoms. Women (odds ratio[OR], 1.31; 95%CI, 0.47-0.97; p=0.032), years of working >10 years (OR, 2.02; 95%CI, 1.47-2.79; p

The outbreak of SARS-CoV-2 in December 2019, led to the ongoing global pandemic of coronavirus disease 2019 (COVID‑19), which has claimed more than a half million lives in a few months. Enormous efforts are being made in developing vaccines and therapeutic treatment to fight against COVID-19. Inactivated SARS-CoV-2 viruses are currently used as vaccine candidates; therefore, it is important to understand the architecture of SARS-CoV-2. We have propagated and purified a clinical strain of SARS-CoV-2 and genetically and structurally characterized β-propiolactone inactivated viruses. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are observed, the majority of viral spikes appear nail-shaped resembling a postfusion state, where S1 protein of the spike has disassociated. Cryo-electron tomography and subtomogram averaging of these spikes yielded a density map which closely matches the overall structure of SARS-CoV S2 spike and their corresponding glycosylation sites. Our findings have major implications in SARS-CoV-2 vaccine design owing to the critical importance of prefusion immunogens. Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality(202002073000002), the National Institutes of Health grant P50AI150481 (P.Z.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z(P.Z.), and the UK Biotechnology and Biological Sciences Research Council grant BB/S003339/1 (P.Z.). Conflict of Interest: The authors declare no competing financial or non-financial interests. Ethical Approval: The research received approval from the Research Ethics Committee of Shenzhen Third People's Hospital, China (approval number: 2020-038). The Research Ethics Committee waived the requirement informed consent before the study started because of the urgent need to collect epidemiological and clinical data. We analyzed the data anonymously.

The European Commission passed Markets in Financial Instruments Directive II (MiFID II), in part, to unbundle brokers’ execution and research services. We empirically examine the effectiveness of MiFID II in achieving this goal and find that the trading volume generated by the brokers that issued recommendation revisions declined significantly after the enactment of MiFID II. In contrast, the aggregate trading volume response to revisions remained the same. Further, we find that the value of recommendation revisions did not change while forecast accuracy and bias improved. Finally, we evaluate the potentially asymmetric effect of MiFID II on brokers and independent research providers and find evidence suggesting that MiFID II helped level the playing field. These results, collectively, suggest that MiFID II was effective in separating research and execution services and leveling the playing field without significantly hurting the quality of sell-side equity research.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) may be a promising therapy for patients with aggressive multiple sclerosis (MS) unresponsive to standard treatments, but similar evidence is still limited. To assess the long-term outcomes in patients with aggressive MS receiving AHSCT with an intermediate intensity conditioning. Methods: This prospective single-center cohort study was conducted in consecutive patients with aggressive MS in the wards of Departments of Neurology and Hematology by a multidisciplinary team on aggressive MS in Xuanwu Hospital of Capital Medical University (Beijing, China) from February 1, 2001 to December 30, 2010. 47 consecutive patients were screened, 9 did not meet inclusion criteria, 1 declined the treatment and 1 had disease activity during study pending, 36 volunteer patients enrolled in the study. The last patient visit was on September 26, 2018, and data analysis was performed between October 15, 2018 and March 18, 2019. All patients received AHSCT with the modified BEAM (carmustine, etoposide, cytarabine, and melphalan) with teniposide instead of etoposide, and regularly assessed by the Expanded Disability Status Scale (EDSS) score and annual relapse rate (ARR). Demographic, treatment-related, and disease-related exposures were collected as variables of interest, including gender, age of onset, disease subtype, duration from MS diagnosis to AHSCT, the baseline EDSS score, number of treatments before transplantation, the highest EDSS score before transplantation, and ARR before transplantation. Primary outcomes were long-term progression-free survival and overall survival, and secondary outcomes were any transplant-related morbidity and severe adverse events. Findings: The median follow-up was 12.5 years (range, 3-17 years). And the 3-, 5-, 10-, and 17-year probabilities of progression-free survival as assessed by EDSS score were 81%, 72%, 44%, and 17%, respectively, whereas overall survival rates were 97%, 92%, 78%, and 63%, respectively. Factor associated with neurological progression-free after the transplantation was age of 25-34 year at disease onset (25-34 vs. 1 vs. ≤1: HR, 12.20; 95% CI, 2.21-67.36) were associated with a longer survival time. No transplant-related morbidity or severe adverse events were reported after the transplantation. Interpretation: Our study with the most extended follow-up period supports the importance of treating aggressive MS by AHSCT and revealed that age at disease onset over 25 years and lower ARR were associated with better outcomes. The results suggest that the appropriate choice of MS patients for AHSCT is critical for winning a better outcome. Funding: This study was supported by research grants from the National Natural Science Foundation of China (81771862, 81571633), the Beijing Natural Science Foundation (KZ201710025017), the Beijing Municipal Hospital Research and Development Plan (PX2017069), the Beijing Hundred, Thousand, and Ten Thousand Talents Project (2017-CXYF-09), the National Key R&D Program of China (2017YFC1310001, 2017YFC0907700), and the Beijing Municipal Science and Technology Project (Z171100000117016). Declaration of Interest: Authors declare no conflict of interest. Ethical Approval: The Ethics Committees of Xuanwu Hospital approved this study.

Background: Solamargine (SM), a natural plant based photochemical has been shown to have anti-cancer properties. However, the underlying mechanism of this effect remains to be determined. Methods: Cell viability and growth were measured via MTT and Cell-Light EdU assays. The expressions of HOTAIR, miR-214-3p andPDPK1 were examined via qRT-PCR and Western blot, respectively. The promoter activity of HOTAIR and PDPK1 were determined using Secrete-Pair Dual Luminescence Assay. Luciferase reporter assays and RNA immunoprecipitation determined the interactions among miR-214-3p, HOTAIR and PDPK1. Exogenous expressions of HOTAIR and PDPK1 were carried out by transient transfection assays. A mouse xenograft tumor model was used to further evaluate the effects of SM in vivo. Findings: SM inhibited the growth of non-small cell lung cancer (NSCLC) cells, which was not observed in cells stably transfected with PDPK1. While silencing of HOTAIR reduced cell growth, over-expression of HOTAIR resisted the SM mediated inhibition of cell growth. SM increased the expression of miR-214-3p and there was a reciprocal interaction between the HOTAIR and miR-214-3p. Furthermore, SM inhibited PDPK1 gene expression and the physical binding of miR-214-3p to PDPK1 3-UTR. MiR-214-3p mimics inhibited PDPK1 expression. Intriguingly, HOTAIR could directly bind to miR-124-3p and sequestered miR-214-3p from the target gene PDPK1. Finally, in a feedback mechanism, over-expression of PDPK1 reduced the HOTAIR and miR-214-3p expressions, and neutralized the SM-inhibited cell growth. Similar results were observed in vivo. Interpretation: SM inhibited NSCLC cell growth through the reciprocal interaction between HOTAIR and miR-214-3p, which ultimately suppressed PDPK1 gene expression. This unveils a novel molecular mechanism underlying the anti-cancer effect of SM in human lung cancer. Funding Statement: This work was supported in part by the grants from the National Nature Scientific Foundation of China (Nos. 81403216, 81673845, 81703551 and 81871863), the Science and Technology Program of Guangzhou (No. 201607010385), the Major Program of National Natural Science Foundation of Guangdong (No. 2018B030311061), the Discipline of Integrated Chinese and Western Medicine in Guangzhou University of Chinese Medicine (No. A1-Af-D018161Z1513), the Special Science and Technology Join fund from Guangdong Provincial Department of Science and Technology-Guangdong Academy of Traditional Chinese Medicine (No. 2014A020221024). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Animal studies were performed according to the protocols approved by the Institutional Animal Care and Use Committee of Guangdong Provincial Hospital of Chinese Medicine (Ethics Approval Number 2017037) and the National Institutes of Health guidelines for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978).

We examine whether underwriters price-up weakly-demanded IPOs to prevent withdrawal. Our empirical strategy exploits a discontinuity in the distribution of IPO prices around the low boundary of the filing range. Offerings with a high ex-ante withdrawal probability that are priced at this boundary are likely priced-up to meet issuers’ reservation prices. We compare the aftermarket returns of these IPOs to the returns of other weakly-demanded offerings where issuers’ reservation prices were likely not binding, and identify a negative 8.4-percentage point differential attributable to the aggressive pricing inherent in setting the price at the low boundary when withdrawal risk is high.

We integrate the housing market and the labor market in a dynamic general equilibrium model with credit and search frictions. The model is confronted with the U.S. macroeconomic time series. Our estimated model can account for two prominent facts observed in the data. First, the land price and the unemployment rate tend to move in opposite directions over the business cycle. Second, a shock that moves the land price is capable of generating large volatility in unemployment. Our estimation indicates that a 10 percent drop in the land price leads to a 0.34 percentage point increase in the unemployment rate (relative to its steady state).

We argue that positive co-movements between land prices and business investment are a driving force behind the broad impact of land-price dynamics on the macroeconomy. We develop an economic mechanism that captures the co-movements by incorporating two key features into a DSGE model: We introduce land as a collateral asset in firms' credit constraints and we identify a shock that drives most of the observed fluctuations in land prices. Our estimates imply that these two features combine to generate an empirically important mechanism that amplifies and propagates macroeconomic fluctuations through the joint dynamics of land prices and business investment.

Previous studies on financial frictions have been unable to establish the empirical significance of credit constraints in macroeconomic fluctuations. This paper argues that the muted impact of credit constraints stems from the absence of a mechanism to explain the observed persistent comovements between housing prices and business investment. We develop such a mechanism by incorporating two key features into a dynamic stochastic general equilibrium model: We identify shocks that shift the demand for collateral assets and allow productive agents to be credit-constrained. A combination of these two features enables our model to successfully generate an empirically important mechanism that amplifies and propagates macroeconomic fluctuations through credit constraints.

This study explores the macroeconomic implications of adaptive expectations in a standard real business cycle model. When rational expectations are replaced by adaptive expectations, we show that the self-confirming equilibrium is the same as the steady-state rational expectations equilibrium for all admissible parameters but that dynamics around the steady state are substantially different between the two equilibria. The differences are driven mainly by the dampened wealth effect and the strengthened intertemporal substitution effect, not by the escapes emphasized by Williams (2003). As a result, adaptive expectations can be an important source of frictions that amplify and propagate technology shocks and seem promising for generating plausible labor market dynamics.