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The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

ABSTRACT: Objectives: To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. Methods: Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. Results: Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). Conclusion: The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.

Cadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.

Summary: Background: In a previous phase 3 clinical trial, we showed that an inactivated poliovirus vaccine derived from the Sabin strain (sIPV) can induce neutralising antibodies against currently circulating and reference wild poliovirus strains. However, the immune persistence of sIPV remains to be evaluated. Methods: In this study, 400 participants who were eligible for an early phase 3 clinical trial (Jan 1, 2012–Aug 31, 2014) in Pingle County, GuanXi Province, China, were initially involved in one site. Of the participants in the previous phase 3 clinical trial, sera of 287, 262, 237, and 207 participants were sampled at the ages of 4, 6, 8, and 10 years, respectively, after the prime-boost regimen. Neutralising antibodies against attenuated Sabin strains were detected using these serum samples to determine immune persistence. The serum neutralising antibodies titre of 1:8 against poliovirus types 1, 2, and 3 is considered to be a seroprotection level for polio. The trial is registered at ClinicalTrials.gov, NCT01510366. Findings: The protective rates against poliovirus types 1, 2, and 3 in the sIPV group were all 100% at 10 years after the booster immunisation, compared with 98.1%, 100%, and 97.1%, respectively, in the wIPV control group after 10 years. After the booster at 18 months, the geometric mean titres (GMTs) of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 13,265.6, 7856.7, and 6432.2, respectively, and the GMTs in the control group (inoculated with inactivated poliovirus vaccine derived from wild strain (wIPV)) were 3915.6, 2842.6, and 4982.7, respectively. With increasing time after booster immunisation, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 gradually decreased in both the sIPV and wIPV groups. At the age of ten years, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 452.3, 392.8, and 347.5, respectively, and the GMTs in the wIPV group 108.5, 154.8, and 229.3, respectively, which were still at a higher-than-protective level (1:8). Interpretation: Both sIPV and wIPV maintained sufficiently high immune persistence against poliovirus types 1, 2, and 3 for at least 10 years after booster immunisation. Funding: Yunnan Provincial Science and Technology Department, the Bill and Melinda Gates Foundation, the National High-tech Research and Development Program, the National International Science and Technology Cooperation Project, the Yunnan Application Basic Research Project, the Innovation Team Project of Xie He, the Yunnan International Scientific and Technological Cooperation Project, and the Medical and Technology Innovation Project of Xie He.

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

Background: We assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer. Methods: This was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8–11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose. Findings: We enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p

Background: The link between schizophrenia and diabetes mellitus is well established by observational studies; however, the cause-effect relationship remains unclear. Methods: Here, we conducted Mendelian randomization analyses to assess a causal relationship of the genetic variants related to elevated fasting glucose levels, hemoglobin A1c (HbA1c), fasting insulin levels, and type 2 diabetes with the risk of schizophrenia. The analyses were performed using summary statistics obtained for the variants identified from the genome-wide association meta-analyses of fasting glucose levels (up to 133,010 individuals), HbA1c (up to 153,377 individuals), fasting insulin levels (up to 108,557 individuals), type 2 diabetes (up to 659,316 individuals), and schizophrenia (up to 108,341 individuals). The association between each variant and schizophrenia was weighted by its association with each studied condition, and estimates were combined using an inverse-variance weighted meta-analysis. Findings: Using information from thirteen variants related to fasting insulin levels, the causal effect of fasting insulin levels increases (per 1-SD) on the risk of schizophrenia was estimated at an odds ratio (OR) of 2·33 (p = 0·001), which is consistent with findings from the observational studies. The fasting glucose associated single nucleotide polymorphisms (SNPs) had no effect on the risk of schizophrenia in Europeans and East Asians (p > 0·05). Nonsignificant effects on the risk of schizophrenia was observed with raised HbA1c and type 2 diabetes, and consistent estimates were obtained across different populations. Interpretation: Our results suggest a causal role of elevated fasting insulin levels in schizophrenia pathogenesis. Keywords: Mendelian randomization, Schizophrenia, Fasting insulin levels, Type 2 diabetes, Hyperglycemia, Hyperinsulinemia

Thermoelectric materials capable of direct conversion between electricity and heat provide a broad prospect for power generation and refrigeration. As a family of potential thermoelectric materials, semiconducting chalcogenide glasses exhibit unique characteristics of easy to draw fiber, high Seebeck coefficient, low thermal conductivity and tunable electrical conductivity, endowing them with promising applications in wearable electronics. In this review, we summarize the recent advance on semiconducting chalcogenide glass for thermoelectric application. The design and fabrication method of semiconducting chalcogenide glasses are presented. The strategies for improving the thermoelectric performance of chalcogenide glasses are reported. Besides, the extensive applications of chalcogenide fibers in the fields of thermal sensing and positioning are overviewed. In the end, the challenges and perspectives for the future development of semiconducting chalcogenide glasses and fibers are discussed.

The Li–S battery is extremely attractive in electric vehicles and portable electronics owing to the ultrahigh theoretical energy density and reduced cost. Nevertheless, sulfur dissolves into polysulfide in the electrolyte and shuttles between the electrodes results in rapid capacity decay, thereby limits practical applications in energy storage. Herein, a simple coating method was proposed to introduce a WS2@PB11 Prussian blue (PB)–PPy22 Polypyrrole (PPy)–modified coating on the surface of the conventional polymer separator. The unparalleled composition of the WS2@PB–PPy layer can adequately inhibit the back and forth of polysulfides and the formation of inactive sulfur–related substances. Therefore, lithium ions can be transferred homogeneously inside the battery. Compared with those of batteries with pristine PP separators, the specific capacity and cycle stability are remarkably ameliorated for lithium-sulfur battery. This modified separator battery exhibits a raised specific capacity (1050 mAh g−1) and promoted capacity retention (650 mAh g−1 after 300 cycles) with coulombic efficiency more than 99.5% and capacity retention rate reaching 62%. It demonstrates that the three-layer porous as ions sieve structure indeed prevents the transfer of polysulfides through electrolyte to the anode and allows lithium-ion to pass through the separator. The rational design for the modified separator provides a trendy method to realize high-performance Li–S batteries.

GexS100-x glasses with a wide compositional range of 10 ≤ x ≤ 43 (mol%) were prepared for the investigation and understanding of compositional trends of physical properties and structural features in this binary chalcogenide glasses. Both of mechanical and thermal properties were studied by the techniques of micro-indentation, resonant ultrasound spectroscopy, dilatometer, and DSC. The compositional evolution of network structure was discussed with the detailed investigation of Raman spectra. The thermo-mechanical properties, including hardness, thermal expansion coefficient, and elastic modulus, are firstly studied systematically in this binary glass system. Together with structural model theories, the correlation between thermo-mechanical properties and network structure of GexS100-x glasses is established. This work further clarify the composition-structure-property relationship of chalcogenide glasses, which would contribute to the compositional design of novel glasses with elaborate properties. Keywords: Chalcogenide glass, Network structure, Mechanical property, Thermal property