GLUT4 mediates the protective function of gastrodin against pressure overload-induced cardiac hypertrophy.

Gastrodia elata exhibits extensive pharmacological activity; its extract gastrodin (GAS) has been used clinically to treat cardiovascular diseases. In the present study, we examined the effect of GAS in a mice model of pathological cardiac hypertrophy, which was induced using transverse aortic constriction (TAC). Male C57BL/6 J mice underwent either TAC or sham surgery. GAS was administered post-surgically for 6 weeks and significantly improved the deterioration of cardiac contractile function caused by pressure overload, cardiac hypertrophy, and fibrosis in mice. Treatment with GAS for 6 weeks upregulated myosin heavy chain α and down-regulated myosin heavy chain ß and atrial natriuretic peptide, while insulin increased the effects of GAS against cardiac hypertrophy. In vitro studies showed that GAS could also protect phenylephrine-induced cardiomyocyte hypertrophy, and these effects were attenuated by BAY-876, and increased by insulin. Taken together, our results suggest that the anti-hypertrophic effect of gastrodin depends on its entry into cardiomyocytes through GLUT4.

Inhibitory mechanism of n-MTAB AuNPs for α-synuclein aggregation.

OBJECTIVE: The aggregation of alpha-synuclein (α-syn) is closely related to the pathogenesis and dysfunction of Parkinson's disease. METHODS: To investigate the potential of nanoparticlemediated therapy, the interactive mechanism between α-syn and n-myristyltrimethylammonium bromide (MTAB) Gold nanoparticles (AuNPs) with different diameters was explored by molecular dynamics simulations. RESULTS: The results indicated that there was a directional interaction between α-syn and n-MTAB AuNPs, in which the driving force for the binding of the C-terminus in α-syn came from electrostatic interactions and the nonamyloid ß component (NAC) domain exhibited weak hydrophobic interactions as well as electrostatic interaction, thereby preventing α-syn aggregation. Energy statistics and analysis showed that for 5-MTAB AuNPs, acidic amino acids such as Glu and Asp played a very important role. CONCLUSIONS: This study not only demonstrated a theoretical foundation for the behavior of biomolecules directionally adsorbed on the surface of biofunctional nanoparticles but also indicated that 5-MTAB AuNPs may be a potential inhibitor against α-syn protein aggregation.

Beyond 300-Gbps/λ photonics-aided THz-over-fiber transmission employing MIMO single-carrier frequency-domain equalizer.

We experimentally realized a 320-GHz 320-Gbps/λ terahertz (THz) radio-over-fiber (RoF) system based on a photonics-aided scheme with the help of polarization-division multiplexing (PDM) technology and multiple-input, multiple-output (MIMO) transmission. In this system, the low-complexity MIMO single-carrier frequency-domain equalizer (SCFDE) is implemented to compensate for the polarization-related impairments of the PDM signal, and the demultiplexing performances between SCFDE and the commonly used constant modulus algorithm (CMA) are also compared in this proposed system. After 20-km standard single-mode fiber (SSMF) and 3-m 2 × 2 MIMO wireless link transmission, the bit error rate (BER) of the received 46-GBaud PDM 16-ary quadrature amplitude modulation (16QAM) signal satisfies the soft-decision forward error correction (SD-FEC) threshold with 15% overhead, which corresponds to a record-breaking net bit rate of 320 Gbit/s.

Ultrathin and Flexible Bioelectronic Arrays for Functional Measurement of iPSC-Cardiomyocytes under Cardiotropic Drug Administration and Controlled Microenvironments.

Emerging heart-on-a-chip technology is a promising tool to establish in vitro cardiac models for therapeutic testing and disease modeling. However, due to the technical complexity of integrating cell culture chambers, biosensors, and bioreactors into a single entity, a microphysiological system capable of reproducing controlled microenvironmental cues to regulate cell phenotypes, promote iPS-cardiomyocyte maturity, and simultaneously measure the dynamic changes of cardiomyocyte function in situ is not available. This paper reports an ultrathin and flexible bioelectronic array platform in 24-well format for higher-throughput contractility measurement under candidate drug administration or defined microenvironmental conditions. In the array, carbon black (CB)-PDMS flexible strain sensors were embedded for detecting iPSC-CM contractility signals. Carbon fiber electrodes and pneumatic air channels were integrated to provide electrical and mechanical stimulation to improve iPSC-CM maturation. Performed experiments validate that the bioelectronic array accurately reveals the effects of cardiotropic drugs and identifies mechanical/electrical stimulation strategies for promoting iPSC-CM maturation.

Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study.

BACKGROUND: Small airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored. METHODS: We conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment. RESULTS: CTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 ± 19.7 vs. 63.8 ± 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p < 0.001 in patients with SAD; 5.13 ± 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters. CONCLUSION: In our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.

Comparison of Animal Models for the Study of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases, and there is still no effective treatment for its advanced stage, nonalcoholic steatohepatitis (NASH). An ideal animal model of NAFLD/NASH is urgently needed for preclinical studies. However, the models reported previously are quite heterogeneous due to differences in animal strains, feed formulations, evaluation indicators, etc. Here, we report five NAFLD mouse models we developed in previous studies and comprehensively compared their characteristics. The high-fat diet (HFD) model is time-consuming and is characterized by early insulin resistance and slight liver steatosis at 12 weeks. Still, inflammation and fibrosis are rare, even at 22 weeks. The high fat, high fructose, and high cholesterol diet (FFC) exacerbates glucose and lipid metabolism disorders, showing distinct hypercholesterolemia, steatosis, and mild inflammation at 12 w. An FFC diet combined with streptozotocin (STZ) is a novel model that speeds up the process of lobular inflammation and fibrosis. The STAM model also used a combination of FFC and STZ but employs newborn mice and shows the fastest formation of fibrosis nodules. The HFD model is appropriate for the study of early NAFLD. FFC combined with STZ accelerates the pathological process of NASH and may be the most promising model for NASH research and drug development.

Current pubertal development in Chinese children and the impact of overnutrition, lifestyle and perinatal factors.

CONTEXT: Pubertal onset has been decreasing in many countries but there has been no data on pubertal development in Chinese children over the last decade. OBJECTIVE: The primary objective of the study was to evaluate the current status of sexual maturation in Chinese children and adolescents. Secondary objectives were to examine socio-economic, lifestyle and auxological associations with pubertal onset. DESIGN: A national, cross-sectional health survey. SETTING: The community-based setting. PARTICIPANTS: A multistage, stratified cluster random sampling method was used to select a nationally representative sample, consisting of 231,575 children and adolescents（123,232 boys and 108,343 girls) between 2017 and 2019. MAIN OUTCOME MEASURE: Growth parameters and pubertal staging were assessed by physical examination. RESULTS: Compared to 10 years previously the median age of Tanner 2 breast development and menarche were similar at 9.65 years and 12.39 years respectively. However, male puberty occurred earlier with a median age of testicular volume ≥4 ml of 10.65 years. Pubertal onset did occur earlier at the extremes with 3.3% of the girls with breast development between 6.5-6.99 years old increasing to 5.8% by 7.5-7.99 years old. Early pubertal onset was also noted in boys, with a testicular volume ≥ 4 ml noted in 1.5% between 7.5-7.99 years increasing to 3.5% between 8.5-8.99 years old. Obesity and overweight increased the risk of developing earlier puberty compared to the normal weight in both boys and girls. CONCLUSIONS: Over the past decade, pubertal development is occurring earlier in Chinese children. While the cause is multifactorial, overweight and obesity are associated with earlier puberty onset. The currently-used normative pubertal data of precocious puberty may not be applicable to diagnose precocious puberty.

Development and validation of a 13-gene signature associated with immune function for the detection of Alzheimer's disease.

Current knowledge of Alzheimer's disease (AD) etiology and effective therapy remains limited. Thus, the identification of biomarkers is crucial to improve the detection and treatment of patients with AD. Using robust rank aggregation method to analyze the microarray data from Gene Expression Omnibus database, we identified 1138 differentially expressed genes in AD. We then explored 13 hub genes by weighted gene co-expression network analysis, least absolute shrinkage, and selection operator, and logistic regression in the training dataset. The detection model, which composed of CD163, CDC42SE1, CECR6, CSF1R, CYP27A1, EIF4E3, H2AFJ, IFIT2, IL10RA, KIAA1324, PSTPIP1, SLA, and TBC1D2 genes, along with APOE gene, showed that the area under the curve for detecting AD was 0.821 (95% confidence interval [CI] = 0.782-0.861) and the model was validated in ADNI dataset (area under the curve = 0.776; 95%CI = 0.686-0.865). Notably, the 13 genes in the model were highly enriched in immune function. These findings have implications for the detection and therapeutic target of AD.

Riemerella anatipestifer Endonuclease I displays enzymatic activity and is associated with bacterial virulence.

Riemerella anatipestifer is an important pathogen of waterfowl, causing septicemic and exudative diseases. We previously reported that the R. anatipestifer AS87_RS02625 is a secretory protein of the type IX secretion system (T9SS). In this study, R. anatipestifer T9SS protein AS87_RS02625 was determined to be a functional Endonuclease I (EndoI), which has DNase and RNase activities. Optimal temperature and pH of the recombinant R. anatipestifer EndoI (rEndoI) to cleave λDNA were determined as 55-60 °C and 7.5 respectively. The DNase activity of the rEndoI was dependent on the presence of divalent metal ions. Presence of Mg2+ at a concentration range of 7.5-15 mM in the rEndoI reaction buffer displayed the highest DNase activity. In addition, the rEndoI displayed RNase activity to cleave MS2-RNA (ssRNA), either in the absence or presence of divalent cations Mg2+, Mn2+, Ca2+, Zn2+ and Cu2+. The DNase activity of the rEndoI was significantly enhanced by Mg2+, Mn2+ and Ca2+ but not Zn2+ and Cu2+. Moreover, we indicated that R. anatipestifer EndoI functioned on the bacterial adherence, invasion, in vivo survival and inducing inflammatory cytokines. These results indicate that the R. anatipestifer T9SS protein AS87_RS02625 is a novel EndoI, displays endonuclease activity and plays an important role in bacterial virulence.

Analyzing and predicting the risk of death in stroke patients using machine learning.

Background: Stroke is an acute disorder and dysfunction of the focal neurological system that has long been recognized as one of the leading causes of death and severe disability in most regions globally. This study aimed to supplement and exploit multiple comorbidities, laboratory tests and demographic factors to more accurately predict death related to stroke, and furthermore, to make inferences about the heterogeneity of treatment in stroke patients to guide better treatment planning. Methods: We extracted data from the Medical Information Mart from the Intensive Care (MIMIC)-IV database. We compared the distribution of the demographic factors between the control and death groups. Subsequently, we also developed machine learning (ML) models to predict mortality among stroke patients. Furthermore, we used meta-learner to recognize the heterogeneity effects of warfarin and human albumin. We comprehensively evaluated and interpreted these models using Shapley Additive Explanation (SHAP) analysis. Results: We included 7,483 patients with MIMIC-IV in this study. Of these, 1,414 (18.9%) patients died during hospitalization or 30 days after discharge. We found that the distributions of age, marital status, insurance type, and BMI differed between the two groups. Our machine learning model achieved the highest level of accuracy to date in predicting mortality in stroke patients. We also observed that patients who were consistent with the model determination had significantly better survival outcomes than the inconsistent population and were better than the overall treatment group. Conclusion: We used several highly interpretive machine learning models to predict stroke prognosis with the highest accuracy to date and to identify heterogeneous treatment effects of warfarin and human albumin in stroke patients. Our interpretation of the model yielded a number of findings that are consistent with clinical knowledge and warrant further study and verification.

MYPT1SMKO Mice Function as a Novel Spontaneous Age- and Hypertension-Dependent Animal Model of CSVD.

Cerebral small vessel disease (CSVD) is the most common progressive vascular disease that causes vascular dementia. Aging and hypertension are major contributors to CSVD, but the pathophysiological mechanism remains unclear, mainly due to the lack of an ideal animal model. Our previous study revealed that vascular smooth muscle cell (VSMC)-specific myosin phosphatase target subunit 1 (MYPT1) knockout (MYPT1SMKO) leads to constant hypertension, prompting us to explore whether hypertensive MYPT1SMKO mice can be considered a novel CSVD animal model. Here, we found that MYPT1SMKO mice displayed age-dependent CSVD-like neurobehaviors, including decreased motion speed, anxiety, and cognitive decline. MYPT1SMKO mice exhibited remarkable white matter injury compared with control mice, as shown by the more prominent loss of myelin at 12 months of age. Additionally, MYPT1SMKO mice were found to exhibit CSVD-like small vessel impairment, including intravascular hyalinization, perivascular space enlargement, and microbleed and blood-brain barrier (BBB) disruption. Last, our results revealed that the brain of MYPT1SMKO mice was characterized by an exacerbated inflammatory microenvironment, which is similar to patients with CSVD. In light of the above structural and functional phenotypes that closely mimic the conditions of human CSVD, we suggest that MYPT1SMKO mice are a novel age- and hypertension-dependent animal model of CSVD.

Metal-Organic Framework Functionalized Bioceramic Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration.

Osteoarthritis (OA) is a degenerative disease that often causes cartilage lesions and even osteochondral damage. Osteochondral defects induced by OA are accompanied by an inflammatory arthrosis microenvironment with overproduced reactive oxygen species (ROS), resulting in the exacerbation of defects and difficulty regenerating osteochondral tissues. Therefore, it is urgently needed to develop osteochondral scaffolds that can not only promote the integrated regeneration of cartilage and subchondral bone, but also possess ROS-scavenging ability to protect tissues from oxidative stress. Herein, zinc-cobalt bimetallic organic framework (Zn/Co-MOF) functionalized bioceramic scaffolds are designed for repairing osteochondral defects under OA environment. By functionalizing Zn/Co-MOF on the 3D-printed beta-tricalcium phosphate (ß-TCP) scaffolds, the Zn/Co-MOF functionalized ß-TCP (MOF-TCP) scaffolds with broad-spectrum ROS-scavenging ability are successfully developed. Benefiting from its catalytic active sites and degradation products, Zn/Co-MOF endows the scaffolds with excellent antioxidative and anti-inflammatory properties to protect cells from ROS invasion, as well as dual-bioactivities of simultaneously inducing osteogenic and chondrogenic differentiation in vitro. Furthermore, in vivo results confirm that MOF-TCP scaffolds accelerate the integrated regeneration of cartilage and subchondral bone in severe osteochondral defects. This study offers a promising strategy for treating defects induced by OA as well as other inflammatory diseases.

Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study.

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

Real-time 100-GbE fiber-wireless seamless integration system using an electromagnetic dual-polarized single-input single-output wireless link at the W band.

This Letter demonstrates a real-time 100-GbE fiber-wireless seamless integration system operating at the whole W band (75-110 GHz). Based on a pair of commercial digital coherent optical modules, the real-time transparent transmission of 125-Gb/s dual-polarized quadrature phase-shift keying signal has been successfully achieved over two-spans of 20-km fiber and up to 150-m electromagnetic dual-polarized single-input single-output wireless link. To the best of our knowledge, this is the first real-time demonstration of 100-GbE signal transmission over >100-m wireless distance at the millimeter-wave band based on photonics. We believed this real-time and high-speed fiber-wireless seamless integration system with a wireless coverage up to hundreds of meters can significantly accelerate the progress of upcoming 6G.

Identification and characterization of extra-chromosomal circular DNA in the silk-gland of Bombyx mori.

The silk-gland cells of silkworm are special cells which only replicate DNA in the nucleus without cell division throughout the larval stage. The extrachromosomal circular DNAs (eccDNAs) have not yet been reported in the silk-gland of the silkworms. Herein, we have explored the characterization of eccDNAs in the posterior silk-gland of silkworms. A total of 35 346 eccDNAs were identified with sizes ranging from 30 bp to 13 569 549 bp. Motif analysis revealed that dual direct repeats are flanking the 5' and 3' breaking points of eccDNA. The sequences exceeding 1kb length in eccDNAs, present palindromic sequence characteristics flanking the 5' and 3' breaking points of the eccDNA. These motifs might support possible models for eccDNA generation. Genomic annotation of the eccDNA population revealed that most eccDNAs (58.6%) were derived from intergenic regions, whereas full or partial genes were carried by 41.4 % eccDNAs. It was found that silk protein genes fib-H, fib-L, and P25, as well as the transcription factors SGF and sage, which play an important regulatory role in silk protein synthesis, could be carried by eccDNAs. GO and KEGG enrichment analyses showed that the genes carried by eccDNAs were mainly associated with the development and metabolism-related signaling pathways. Moreover, it was found that eccDNAfib-L could promote the transcription of fib-L gene. Overall, the results of the present study not only provide a novel perspective on the mechanism of silk gland development and silk protein synthesis but also complement previously reported genome-scale eccDNA data supporting that eccDNAs are common in eukaryotes. This article is protected by copyright. All rights reserved.

Guanidinium-Rich Lipopeptide-Based Nanoparticle Enables Efficient Gene Editing in Skeletal Muscles.

Genome editing mediated by the CRISPR-Cas system holds great promise for the treatment of genetic diseases. However, safe and efficient in vivo delivery of CRISPR genome editing machinery remains a challenge. Here, we report a lipopeptide-based nanoparticle (LNP) that can efficiently deliver the CRISPR Cas9/sgRNA ribonucleoprotein (RNP) and enable efficient genome editing both in vitro and in vivo. An artificial lipopeptide, GD-LP, was constructed by linking a hydrophilic guanidinium-rich head to an oleic acid-based hydrophobic tail via a disulfide bond. LNP formed by the self-assembly of GD-LP can easily form a complex with RNP with a loading content of up to 20 wt %. The resulting RNP-LNP nanocomplex led to 72.6% gene editing efficiency in GFP-HEK cells with negligible cytotoxicity. The LNP also showed significantly higher transfection efficiencies than Lipofectamine 2000 for the delivery of mRNA in NIH 3T3 and RAW 264.7 and the delivery of plasmid DNA in B78 cells. In vivo studies showed that intramuscular injection of the RNP-LNP nanocomplex in Ai14 mice induced efficient gene editing in muscular tissues. Moreover, the delivery of Cas9 RNP and donor DNA by LNP (i.e., RNP/ssODN-LNP nanocomplex) restored dystrophin expression, reduced skeletal muscle fibrosis, and significantly improved muscle strength in a Duchenne muscular dystrophy (DMD) mouse model.

Does mandibular advancement with clear aligners have the same skeletal and dentoalveolar effects as traditional functional appliances?

BACKGROUND: The study aimed to compare the dentoskeletal effects of Vanbeek Activator, Herbst, Twin-Block and Mandibular Advancement with clear aligners in children with skeletal Class II malocclusions. METHODS: A sample with sixty-three patients (37 males, 26 females) was included and divided into untreated control group (C, n = 12), Vanbeek Activator group (V, n = 14), Herbst group (H, n = 11), Twin-Block group (TB, n = 12) and MA group (MA, n = 14). Cephalometric analysis and Johnston Pitchfork analysis were performed to quantify the skeletal and dentoalveolar components in molar relationship and overjet correction. Compare the differences of cephalometric data and Johnston-analysis data. RESULTS: The treatment changes showed significant differences in SNB, FH-NP, NA-PA, Co-Go, Co-Pog, ANB, lower facial height ratio, U1-PP, U6-PP, L1-MP and U1-L1. All the appliances improved overjet relationships significantly (Vanbeek, Herbst, Twin-Block and MA were 2.77 mm, 5.53 mm, 4.73 mm and 3.66 mm respectively) with significant retraction of maxillary incisors. The lower incisor displacement of group V and MA was negative, while that of group H and TB was positive and there were significant differences. Molar relationships were also improved by 3.45 mm, 6.85 mm, 3.48 mm and 0.92 mm for Vanbeek, Herbst, Twin-Block and MA. Mandible displacement showed a trend of group H > TB > V > MA. The displacement of maxillary molars in group H was greater than that in group C, TB and MA, and that of mandibular ones was greater than that in group C, V and MA, significantly. Herbst, Twin-Block and MA have more significant dentoalveolar effect than Vanbeek, while Vanbeek has more skeletal effect than the others especially in restraining maxillary growth. CONCLUSIONS: Four appliances are all effective in mandibular advancement, modification of class II molar relationship and deep overjet, with unavoidable increase in lower facial ratio. Vanbeek Activator has the most skeletal effects. Vanbeek and MA have a good control of mandibular incisors while more compensatory lower incisors proclination in Herbst and Twin-Block. Herbst has greater maxillary molar distalization. MA allows aligning and leveling meanwhile leading the mandible forward.

The pathological characters of islets aging in old rhesus monkeys.

The loss of ß cell mass and function in aged population plays a critical role in the prevalence of Type 2 diabetes. However, the causal relations between aging and age-related pancreatic islets degeneration still have not been fully elucidated. Rhesus monkey is one of the most ideal nonhuman primate animal models of a wide range of human diseases, including diabetes and aging-related diseases. In the present study, we observed the overall physiological function, glycolipid metabolism and islet function of middle-age and elderly rhesus monkeys, and compared their gene expression profiles by transcriptome sequencing of isolated islets. Through these analyses, we are aimed to evaluate the pathological characters of islets of old rhesus monkeys in the process of aging, and to provide some tips for the prevention and treatment of diabetes in the elderly population. The results suggested that there was no significant physiological disorder in monkeys of approximately 20 years old, except the glucose metabolism was mildly disturbed. In pancreas tissues and isolated islets of elderly monkeys, we found that the islets sizes were distinctly decreased, and the insulin secretion was compromised. Notably, the islets fibrosis and proportion of insulin/glucagon co-expressing cells increased significantly. Moreover, the ß cell identity markers, transcription factors PDX1 and Nkx6.1 were losing with advancing age. Analysis of the RNA sequencing of isolated islets showed the genes related to type 1 diabetes and ß cell function changed markedly. In conclusion, we found that in the elderly monkeys around 20 years old, the decreased islets size and compromised insulin secretion may contribute to the disturbed glucose metabolism, and the loss of ß cell identity markers is a typical molecular change of islet senescence.

Silver lining to a climate crisis in multiple prospects for alleviating crop waterlogging under future climates.

Extreme weather events threaten food security, yet global assessments of impacts caused by crop waterlogging are rare. Here we first develop a paradigm that distils common stress patterns across environments, genotypes and climate horizons. Second, we embed improved process-based understanding into a farming systems model to discern changes in global crop waterlogging under future climates. Third, we develop avenues for adapting cropping systems to waterlogging contextualised by environment. We find that yield penalties caused by waterlogging increase from 3-11% historically to 10-20% by 2080, with penalties reflecting a trade-off between the duration of waterlogging and the timing of waterlogging relative to crop stage. We document greater potential for waterlogging-tolerant genotypes in environments with longer temperate growing seasons (e.g., UK, France, Russia, China), compared with environments with higher annualised ratios of evapotranspiration to precipitation (e.g., Australia). Under future climates, altering sowing time and adoption of waterlogging-tolerant genotypes reduces yield penalties by 18%, while earlier sowing of winter genotypes alleviates waterlogging by 8%. We highlight the serendipitous outcome wherein waterlogging stress patterns under present conditions are likely to be similar to those in the future, suggesting that adaptations for future climates could be designed using stress patterns realised today.

Time series analysis revealed prognostic value of continuous nasopharyngeal SARS-CoV-2 nucleic acid quantification for COVID-19: A retrospective study of >3000 COVID-19 patients from 2 centers.

BACKGROUND: Early stratification of disease progression remains one of the major challenges towards the post-coronavirus disease 2019 (COVID-19) era. The clinical relevance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid load is debated due to the heterogeneity in patients' underlying health conditions. We determined the prognostic value of nasopharyngeal viral load dynamic conversion for COVID-19. METHODS: The cycling threshold (Ct) values of 28,937 nasopharyngeal SARS-CoV-2 RT-PCRs were retrospectively collected from 3,364 COVID-19 patients during hospitalization and coordinated to the onset of disease progression. The ROC curve was utilized to determine the predictive performance of the rate of Ct value alteration between two consecutive RT-PCR runs within 48 h (ΔCt%) for disease transformation across patients with different COVID-19 severity and immune backgrounds, and further validated with 1,860 SARS-CoV-2 RT-PCR results from an independent validation cohort of 262 patients. For the 67 patients with severe COVID-19, Kaplan-Meier analysis was performed to evaluate the difference in survival between patients stratified by the magnitude of Ct value alteration between the late and early stages of hospitalization. RESULTS: The kinetics of viral nucleic acid conversion diversified across COVID-19 patients with different clinical characteristics and disease severities. The ΔCt% is a clinical characteristic- and host immune status-independent indicator for COVID-19 progression prediction (AUC = 0.79, 95 % CI = 0.76 to 0.81), which outperformed the canonical blood test markers, including c-reactive protein (AUC = 0.57, 95 % CI = 0.53 to 0.61), serum amyloid A (AUC = 0.61, 95 % CI = 0.54 to 0.68), lactate dehydrogenase (AUC = 0.61, 95 % CI = 0.56 to 0.67), d-dimer (AUC = 0.56, 95 % CI = 0.46 to 0.66), and lymphocyte count (AUC = 0.62, 95 % CI = 0.58 to 0.66). Patients with persistent high SARS-CoV-2 viral load (an increase of mean Ct value < 50 %) during the first 3 days of hospitalization demonstrated a significantly unfavorable survival (HR = 0.16, 95 % CI = 0.04 to 0.65, P = 2.41 × 10-3). CONCLUSIONS: Viral nucleic acid dynamics of SARS-CoV-2 eliminates the inter-patient variance of basic health conditions and therefore, can serve as a prognostic marker for COVID-19.