The Effects of Poria cocos Polysaccharides on Growth Performance, Immunity, and Cecal Microflora Composition of Weaned Piglets.

This paper aims to identify Poria cocos polysaccharides (PCPs) as a potential feed additive used for swine production; thus, we explored the effects of different dietary inclusion levels of PCP on growth performance, immunity, and cecal microflora composition in weaned piglets. For this, a total of 120 28-day-old Duroc × Landrace × Yorkshire weaned piglets (8.51 ± 0.19 kg; 28 ± 1 days of age) were randomly allocated to five groups that were fed a basal diet supplemented with 0, 0.025%, 0.05%, 0.1%, and 0.2% PCP, respectively, for 42 days. The results indicated that the average daily gain (ADG) and gain/feed ratio were higher in the PCP treatment groups than in the control group, with a linear effect. The serum concentrations of IgG, IgA, IL-2, IFN-γ, the number of CD4+ T cells, and the CD4+-to-CD8+ T-cell ratio (CD4+/CD8+) were increased, while the levels of IL-6 and TNF-α were decreased in the PCP supplementation groups compared with those in the control group. Furthermore, the cytokine mRNA expression levels exhibited a similar trend in the spleen. PCP supplementation also reduced the abundance of Escherichia coli and Salmonella and enhanced that of Lactobacilli and Bifidobacteria in the cecum. In summary, dietary PCP inclusion exerted positive effects on the growth performance, immunity, and cecal microbiota of piglets and showed potential for use as a feed additive for improving the health of weaned piglets, with 0.1% being the optimal dosage.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2=0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.

Comparison of Growth Performance, Carcass Properties, Fatty Acid Profile, and Genes Involved in Fat Metabolism in Nanyang and Landrace Pigs.

This study compared the growth, carcass properties, fatty acid profile, lipid-producing enzyme activity, and expression pattern of genes involved in fat metabolism in Nanyang and Landrace pigs. In the study, 32 Nanyang (22.16 ± 0.59 kg) and 32 Landrace barrows (21.37 ± 0.57 kg) were selected and divided into two groups, each with eight pens and four pigs per pen. The trial period lasted 90 days. The findings showed that the Nanyang pigs had lower average daily weight gain and lean percentage and higher average backfat thickness and lipogenic enzyme activities, including for acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase, than the Landrace pigs. A total of 14 long-chain fatty acids were detected using HPLC-MS, in which it was found that the levels of C14:0, C18:1n-9, C20:1n-9, C20:4n-6, and MUFA were up-regulated and C18:2n-6, C18:3n-3, PUFA n6, n3/n6, and total PUFA were down-regulated in the Nanyang pigs. Moreover, the mRNA levels for genes involved in fat metabolism, ME1, FAS, and LPL, were higher and the expression of SREBP1 mRNA was lower in the Nanyang pigs. Our results suggest genetic differences between the pig breeds in terms of growth, carcass traits, lipogenic enzyme activities, fatty acid profile, and the mRNA expression of genes involved in fat metabolism in subcutaneous fat tissue, which may provide a basis for high-quality pork production. Further studies are needed to investigate the regulation of lipid metabolism.

Associations of a multidimensional polygenic sleep health score and a sleep lifestyle index on health outcomes and their interaction in a clinical biobank.

Sleep is a complex behavior regulated by genetic and environmental factors, and is known to influence health outcomes. However, the effect of multidimensional sleep encompassing several sleep dimensions on diseases has yet to be fully elucidated. Using the Mass General Brigham Biobank, we aimed to examine the association of multidimensional sleep with health outcomes and investigate whether sleep behaviors modulate genetic predisposition to unfavorable sleep on mental health outcomes. First, we generated a Polygenic Sleep Health Score using previously identified single nucleotide polymorphisms for sleep health and constructed a Sleep Lifestyle Index using data from self-reported sleep questions and electronic health records; second, we performed phenome-wide association analyses between these indexes and clinical phenotypes; and third, we analyzed the interaction between the indexes on prevalent mental health outcomes. Fifteen thousand eight hundred and eighty-four participants were included in the analysis (mean age 54.4; 58.6% female). The Polygenic Sleep Health Score was associated with the Sleep Lifestyle Index (ß=0.050, 95%CI=0.032, 0.068) and with 114 disease outcomes spanning 12 disease groups, including obesity, sleep, and substance use disease outcomes (p<3.3×10-5). The Sleep Lifestyle Index was associated with 458 disease outcomes spanning 17 groups, including sleep, mood, and anxiety disease outcomes (p<5.1×10-5). No interactions were found between the indexes on prevalent mental health outcomes. These findings suggest that favorable sleep behaviors and genetic predisposition to healthy sleep may independently be protective of disease outcomes. This work provides novel insights into the role of multidimensional sleep on population health and highlights the need to develop prevention strategies focused on healthy sleep habits.

Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases.

BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9 hours), short (<6 hours), and long (>9 hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355 901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ß=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.

Unlocking Dysprosium Constraints for China's 1.5 °C Climate Target.

Some key low-carbon technologies, ranging from wind turbines to electric vehicles, are underpinned by the strong rare-earth-based permanent magnets of the Nd, Pr (Dy)-Fe-Nb type (NdFeB). These NdFeB magnets, which are sensitive to demagnetization with temperature elevation (the Curie point), require the addition of variable amounts of dysprosium (Dy), where an elevation of the Curie point is needed to meet operational conditions. Given that China is the world's largest REE supplier with abundant REE reserves, the impact of an ambitious 1.5 °C climate target on China's Dy supply chain has sparked widespread concern. Here, we explore future trends and innovation strategies associated with the linkage between Dy and NdFeBs under various climate scenarios in China. We find China alone is expected to exhaust the global present Dy reserve within the next 2-3 decades to facilitate the 1.5 °C climate target. By implementing global available innovation strategies, such as material substitution, reduction, and recycling, it is possible to avoid 48%-68% of China's cumulative demand for Dy. Nevertheless, ongoing efforts in REE exploration and production are still required to meet China's growing Dy demand, which will face competition from the United States, European Union, and other countries with ambitious climate targets. Thus, our analysis urges China and those nations to form wider cooperation in REE supply chains as well as in NdFeB innovation for the realization of a global climate-safe future.

Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.

BACKGROUND: Our previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC. METHODS: Differential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway. RESULTS: A total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC. CONCLUSIONS: There was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.

3D integration enables ultralow-noise isolator-free lasers in silicon photonics.

Photonic integrated circuits are widely used in applications such as telecommunications and data-centre interconnects1-5. However, in optical systems such as microwave synthesizers6, optical gyroscopes7 and atomic clocks8, photonic integrated circuits are still considered inferior solutions despite their advantages in size, weight, power consumption and cost. Such high-precision and highly coherent applications favour ultralow-noise laser sources to be integrated with other photonic components in a compact and robustly aligned format-that is, on a single chip-for photonic integrated circuits to replace bulk optics and fibres. There are two major issues preventing the realization of such envisioned photonic integrated circuits: the high phase noise of semiconductor lasers and the difficulty of integrating optical isolators directly on-chip. Here we challenge this convention by leveraging three-dimensional integration that results in ultralow-noise lasers with isolator-free operation for silicon photonics. Through multiple monolithic and heterogeneous processing sequences, direct on-chip integration of III-V gain medium and ultralow-loss silicon nitride waveguides with optical loss around 0.5 decibels per metre are demonstrated. Consequently, the demonstrated photonic integrated circuit enters a regime that gives rise to ultralow-noise lasers and microwave synthesizers without the need for optical isolators, owing to the ultrahigh-quality-factor cavity. Such photonic integrated circuits also offer superior scalability for complex functionalities and volume production, as well as improved stability and reliability over time. The three-dimensional integration on ultralow-loss photonic integrated circuits thus marks a critical step towards complex systems and networks on silicon.

Experimental realization of convolution processing in photonic synthetic frequency dimensions.

Convolution is an essential operation in signal and image processing and consumes most of the computing power in convolutional neural networks. Photonic convolution has the promise of addressing computational bottlenecks and outperforming electronic implementations. Performing photonic convolution in the synthetic frequency dimension, which harnesses the dynamics of light in the spectral degrees of freedom for photons, can lead to highly compact devices. Here, we experimentally realize convolution operations in the synthetic frequency dimension. Using a modulated ring resonator, we synthesize arbitrary convolution kernels using a predetermined modulation waveform with high accuracy. We demonstrate the convolution computation between input frequency combs and synthesized kernels. We also introduce the idea of an additive offset to broaden the kinds of kernels that can be implemented experimentally when the modulation strength is limited. Our work demonstrate the use of synthetic frequency dimension to efficiently encode data and implement computation tasks, leading to a compact and scalable photonic computation architecture.

Broadband quantum-dot frequency-modulated comb laser.

Frequency-modulated (FM) laser combs, which offer a quasi-continuous-wave output and a flat-topped optical spectrum, are emerging as a promising solution for wavelength-division multiplexing applications, precision metrology, and ultrafast optical ranging. The generation of FM combs relies on spatial hole burning, group velocity dispersion, Kerr nonlinearity, and four-wave mixing (FWM). While FM combs have been widely observed in quantum cascade Fabry-Perot (FP) lasers, the requirement for a low-dispersion FP cavity can be a challenge in platforms where the waveguide dispersion is mainly determined by the material. Here we report a 60 GHz quantum-dot (QD) mode-locked laser in which both the amplitude-modulated (AM) and the FM comb can be generated independently. The high FWM efficiency of -5 dB allows the QD laser to generate FM comb efficiently. We also demonstrate that the Kerr nonlinearity can be practically engineered to improve the FM comb bandwidth without the need for GVD engineering. The maximum 3-dB bandwidth that our QD platform can deliver is as large as 2.2 THz. This study gives novel insights into the improvement of FM combs and paves the way for small-footprint, electrically pumped, and energy-efficient frequency combs for silicon photonic integrated circuits (PICs).

Umbilical cord mesenchymal stem cells overexpressing CXCR7 facilitate treatment of ARDS-associated pulmonary fibrosis via inhibition of Notch/Jag1 mediated by the Wnt/ß-catenin pathway.

The therapeutic efficacy of umbilical cord mesenchymal stem cells (UCMSCs) in acute respiratory distress syndrome (ARDS) is mainly limited by the efficiency of homing of UCMSCs toward tissue damage. C-X-C chemokine receptor type 7 (CXCR7), which is involved in the mobilization of UCMSCs, is only expressed on the surface of a small proportion of UCMSCs. This study examined whether overexpression of CXCR7 in UCMSCs (UCMSCsOE-CXCR7) could improve their homing efficiency, and therefore, improve their effectiveness in fibrosis repair at the site of lung injury caused by ARDS. A lentiviral vector expressing CXCR7 was built and then transfect into UCMSCs. The impacts of CXCR7 expression of the proliferationand homing of UCMSCs were examined in a lipopolysaccharide-induced ARDS mouse model. The potential role and underlying mechanism of CXCR7 were examined by performing scratch assays, transwell assays, and immunoassays. The therapeutic dose and treatment time of UCMSCsOE-CXCR7 were directly proportional to their therapeutic effect on lung injury. In addition, overexpression of CXCR7 increased SDF-1-induced proliferation and migration of lung epithelial cells (Base-2b cells), and upregulation of CXCR7 inhibited α-SMA expression, suggesting that CXCR7 may have a role in alleviating pulmonary fibrosis caused by ARDS. Overexpression of CXCR7 in UCMSCs may improve their therapeutic effect of acute lung injury mouse, The mechanism of fibrosis repair by CXCR7 is inhibition of Jag1 via suppression of the Wnt/ß-catenin pathway under the chemotaxis of SDF-1.

Associations between sleep health and grey matter volume in the UK Biobank cohort (n = 33 356).

As suggested by previous research, sleep health is assumed to be a key determinant of future morbidity and mortality. In line with this, recent studies have found that poor sleep is associated with impaired cognitive function. However, to date, little is known about brain structural abnormalities underlying this association. Although recent findings link sleep health deficits to specific alterations in grey matter volume, evidence remains inconsistent and reliant on small sample sizes. Addressing this problem, the current preregistered study investigated associations between sleep health and grey matter volume (139 imaging-derived phenotypes) in the UK Biobank cohort (33 356 participants). Drawing on a large sample size and consistent data acquisition, sleep duration, insomnia symptoms, daytime sleepiness, chronotype, sleep medication and sleep apnoea were examined. Our main analyses revealed that long sleep duration was systematically associated with larger grey matter volume of basal ganglia substructures. Insomnia symptoms, sleep medication and sleep apnoea were not associated with any of the 139 imaging-derived phenotypes. Short sleep duration, daytime sleepiness as well as late and early chronotype were associated with solitary imaging-derived phenotypes (no recognizable pattern, small effect sizes). To our knowledge, this is the largest study to test associations between sleep health and grey matter volume. Clinical implications of the association between long sleep duration and larger grey matter volume of basal ganglia are discussed. Insomnia symptoms as operationalized in the UK Biobank do not translate into grey matter volume findings.

Quantum decoherence of dark pulses in optical microresonators.

Quantum fluctuations disrupt the cyclic motions of dissipative Kerr solitons (DKSs) in nonlinear optical microresonators and consequently cause timing jitter of the emitted pulse trains. This problem is translated to the performance of several applications that employ DKSs as compact frequency comb sources. Recently, device manufacturing and noise reduction technologies have advanced to unveil the quantum properties of DKSs. Here we investigate the quantum decoherence of DKSs existing in normal-dispersion microresonators known as dark pulses. By virtue of the very large material nonlinearity, we directly observe the quantum decoherence of dark pulses in an AlGaAs-on-insulator microresonator, and the underlying dynamical processes are resolved by injecting stochastic photons into the microresonators. Moreover, phase correlation measurements show that the uniformity of comb spacing of quantum-limited dark pulses is better than 1.2 × 10-16 and 2.5 × 10-13 when normalized to the optical carrier frequencies and repetition frequencies, respectively. Comparing DKSs generated in different material platforms explicitly confirms the advantages of dark pulses over bright solitons in terms of quantum-limited coherence. Our work establishes a critical performance assessment of DKSs, providing guidelines for coherence engineering of chip-scale optical frequency combs.

Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study.

Co-infection in patients with severe fever with thrombocytopenia syndrome (SFTS) has been reported, posing a serious threat to survival and treatment. We aimed to systematically investigate the SFTS associated pulmonary infection, particularly invasive pulmonary fungal infection (IPFI). During April 2019 to October 2021, we conducted a multicentre observational study on adult hospitalized patients confirmed with SFTS from three tertiary hospital in central China. Demographic, clinical and laboratory data of patients were collected and re-assessed. A total of 443 patients (51.7% were male sex) were included for analysis with median age of 65-year-old. Among them, 190 (42.9%) patients met the criteria for pulmonary infection. Pulmonary infection was associated with shorter survival time (p < 0.0001 by log-rank test), and adjusted hazard ratio was 1.729 [95% confidence interval, 1.076-2.780] (p = 0.024). Age (odds ratio (OR) 1.040 [1.019-1.062], p < 0.001), time from onset to admission (OR 1.163 [1.070-1.264], p < 0.001), having severe status (OR 3.166 [2.020-4.962], p < 0.001) and symptoms of skin change (OR 2.361 [1.049-5.316], p < 0.001) at admission and receiving intravenous immunoglobin (OR 2.185 [1.337-3.569], p = 0.002) were independent risk factors for the occurrence of pulmonary infection. A total of 70 (15.8%) patients were defined as IPFI. Multivariate analysis showed that time from onset to admission (OR 1.117 [1.016-1.229], p = 0.022), severe status (OR 5.737 [3.054-10.779], p < 0.001), having smoking history (OR 3.178 [1.251-8.070], p = 0.015) and autoimmunity disease (OR 7.855 [1.632-37.796], p = 0.010), receiving intravenous immunoglobin (OR 3.270 [1.424-7.508], p = 0.005) were independent risk factors for the occurrence of IPFI. In SFTS patients with pulmonary infection, white blood count <2.09 × 109 per L (OR 11.064 [3.708-33.012], p < 0.001) and CD3+ CD4+ T cell count <104.0 per µL (OR 10.429 [3.395-32.038], p < 0.001) could independently predict IPFI. This study showed the high prevalence and poor outcomes of pulmonary infection and IPFI in patients with SFTS. These findings highlighted the need for active surveillance of fungal pathogens and early antifungal treatment in patients with SFTS.

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-ß/SMAD signaling.

BACKGROUND AND AIMS: Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis. METHODS AND RESULTS: The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-ß-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-ß/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-ß, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)-mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)-mediated TrkB overexpression in hepatocytes. CONCLUSION: TGF-ß stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-ß/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo . These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.

Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial.

BACKGROUND: Tecarfarin (ATI-5923), a structural analog of warfarin, was designed to provide more uniform and stable anticoagulation. OBJECTIVE: We aimed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of tecarfarin when administered in multiple ascending doses (MADs) to healthy Chinese volunteers. METHODS: Forty healthy Chinese volunteers were enrolled into four sequential cohorts (10, 20, 30, and 40 mg), with 10 subjects in each cohort. Participants in the MAD study for each sequential cohort were dose-titrated to achieve the target international normalized ratio (INR 1.7-2.0) for 14 days. Safety and tolerability were assessed throughout the study. RESULTS: The pharmacokinetic and pharmacodynamic profile of tecarfarin was investigated in a healthy Chinese population. Dose titration of tecarfarin was necessary to keep the INR in the target range in all subjects in the 20, 30 and 40 mg cohorts and a few subjects (n = 3) in the 10 mg cohort. Tecarfarin was well tolerated without serious adverse events. Only one treatment-related adverse event (hematochezia) resulted in early withdrawal from the MAD 40 mg cohort. CONCLUSION: Tecarfarin was well-tolerated by Chinese volunteers. Dose titration was needed for tecarfarin doses larger than 20 mg to keep the INR in the target range. REGISTRATION: ClinicalTrials.gov identifier: NCT04627116.

An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling.

Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find differential gene expression by blood cell type in relation to SDB traits and link P2XR4 expression to average oxyhemoglobin saturation during sleep and butyrylcarnitine (C4) levels. These findings can be used to develop interventions to alleviate the effect of SDB on the human molecular environment.

Genetic associations between sleep traits and cognitive ageing outcomes in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults. METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value <0.05. FINDINGS: Higher PRS for insomnia was associated with lower global cognitive function and higher risk of mild cognitive impairment (MCI) (OR = 1.20, 95% CI [1.06, 1.36]). Higher PRS for daytime sleepiness was also associated with increased MCI risk (OR = 1.14, 95% CI [1.02, 1.28]). Sleep duration PRS was associated with reduced MCI risk among short and normal sleepers, while among long sleepers it was associated with reduced global cognitive function and with increased MCI risk (OR = 1.40, 95% CI [1.10, 1.78]). Furthermore, adjustment of analyses for the measured sleep phenotypes and APOE-ε4 allele had minor effects on the PRS associations with the cognitive outcomes. INTERPRETATION: Genetic measures underlying insomnia, daytime sleepiness, and sleep duration are associated with MCI risk. Genetic and self-reported sleep duration interact in their effect on MCI. FUNDING: Described in Acknowledgments.

Cascading impacts of global metal mining on climate change and human health caused by COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted global metal mining and associated supply chains. Here we analyse the cascading effects of the metal mining disruption associated with the COVID-19 pandemic on the economy, climate change, and human health. We find that the pandemic reduced global metal mining by 10-20% in 2020. This reduction subsequently led to losses in global economic output of approximately 117 billion US dollars, reduced CO2 emissions by approximately 33 million tonnes (exceeding Hungary's emissions in 2015), and reduced human health damage by 78,192 disability-adjusted life years. In particular, copper and iron mining made the most significant contribution to these effects. China and rest-of-the-world America were the most affected. The cascading effects of the metal mining disruption associated with the pandemic on the economy, climate change, and human health should be simultaneously considered in designing green economic stimulus policies.