Variety Is the Spice of Life: Diverse Social Networks Are Associated With Social Cohesion and Well-Being.

Both homophily and heterophily are observed in humans. Homophily reinforces homogeneous social networks, and heterophily creates new experiences and collaborations. However, at the extremes, high levels of homophily can cultivate prejudice toward out-groups, whereas high levels of heterophily can weaken in-group support. Using data from 24,726 adults (M = 46 years; selected from 10,398 English neighborhoods) and the composition of their social networks based on age, ethnicity, income, and education, we tested the hypothesis that a middle ground between homophily and heterophily could be the most beneficial for individuals. We found that network homophily, mediated by perceived social cohesion, is associated with higher levels of subjective well-being but that there are diminishing returns, because at a certain point increasing network homophily is associated with lower social cohesion and, in turn, lower subjective well-being. Our results suggest that building diverse social networks provides benefits that cannot be attained by homogeneous networks.

Lessons on food security from the COVID-19 pandemic in Bermuda.

Compared with other OECD countries, Bermuda ranks third globally in terms of income inequality globally. During the COVID-19 pandemic, anecdotal evidence suggested, significant fluctuations in the food demand and supply. We aimed to examine the impact of the COVID-19 pandemic on food insecurity, with a focus on the availability and affordability of various foods in Bermuda. We utilized a cross-sectional study design to investigate potential drivers of food insecurity within the local population. To gauge the level of household food insecurity we relied on the Bermuda Omnibus survey (N = 400) undertaken by Total Research Associates Ltd via telephone. To assess changes in food availability and affordability we conducted semi-structured interviews with key stakeholders who played pivotal roles in shaping food accessibility availability and affordability of food in Bermuda. These interviews were systematically analysed using the framework method. We performed analyses of food retail and import data to evaluate fluctuations in food prices and their impact on food availability and affordability. We found statistically significant associations between changes in food consumption, household income, and government aid. Food aid beneficiaries ate fewer fruits and vegetables by 50% [95% CI:17%-83%] and less fresh meat and fish by 39% [95 CI:3%-75%] compared with residents who did not receive any aid during the COVID-19 period from March 2020 to March 2021. Although we did not identify statistically significant food price increases feeding programmes played a pivotal role in preventing food insecurity during the pandemic in Bermuda. However, a lack of monitoring regarding the nutritional quality within the programmes, allowed a wide availability of foods high in sugar, salts, and fats, disproportionately affected low-income populations. In conclusion, food availability in Bermuda remained largely unaffected during the pandemic. Nevertheless, the surge in demand for feeding programs underscores underlying food security challenges in Bermuda and warrants further attention.

Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer.

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.

Lower tacrolimus time in therapeutic range is associated with inferior outcomes in adult liver transplant recipients.

Previous studies on solid organ transplantation have reported that a low time in therapeutic range (TTR) of tacrolimus increases the risk of poor outcomes. However, the reproducibility of the findings in liver transplantation has not yet been confirmed. The TTR, coefficient of variation (CV) and standard deviation (SD) were calculated for 207 adult liver transplant patients from the date of transplantation until the first episode of acute rejection (AR), graft loss, acute kidney injury (AKI), biliary complications, infection or the last follow-up. Kaplan-Meier curves, log-rank tests and Cox regression analyses were performed. Sixty-one (29.5%) patients reached the composite endpoint of AR, biliary complications and graft loss. The log-rank test indicated that the low TTR group had an increased risk of the composite endpoint (P < 0.001), AKI (P < 0.001) and infection (P < 0.001). Multivariate Cox regression analyses revealed that a 10% decrease in TTR was associated with an increased hazard for composite endpoint (hazard ratio [HR]: 1.185, P = 0.010), AKI (HR: 1.355, P < 0.001) and infection (HR: 1.357, P < 0.001). Unexpectedly, SD and CV demonstrated no association with the above-mentioned inferior outcomes. Compared with SD and CV, the TTR of tacrolimus was more correlated with inferior outcomes and may be a novel indicator for predicting the prognosis of liver transplantation.

Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients.

Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the study was to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients by using a global metabolomic approach. A total of 693 plasma samples were collected from 137 liver transplant recipients receiving tacrolimus and regular therapeutic drug monitoring. Untargeted metabolomic analysis was performed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses with a mixed linear model were conducted, and the results showed that the dose-adjusted tacrolimus trough concentration was associated with 31 endogenous metabolites, including medium- and long-chain acylcarnitines such as stearoylcarnitine (ß = 0.222, p = 0.001), microbiota-derived uremic retention solutes such as indolelactic acid (ß = 0.194, p = 0.007), bile acids such as taurohyodeoxycholic acid (ß = -0.056, p = 0.002), and steroid hormones such as testosterone (ß = 0.099, p = 0.001). A multiple linear mixed model including 11 metabolites and clinical information was established with a suitable predictive performance (correlation coefficient based on fixed effects = 0.64 and correlation coefficient based on fixed and random effects = 0.78). These data demonstrated that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients.

Synergistic Catalysis by Single-Atom Catalysts and Redox Mediator to Improve Lithium-Oxygen Batteries Performance.

Lithium-oxygen (Li-O2 ) batteries with ultrahigh theoretical energy density have attracted widespread attention while there are still problems with high overpotential and poor cycle stability. Rational design and application of efficient catalysts to improve the performance of Li-O2 batteries is of significant importance. In this work, Co single atoms catalysts are successfully combined with redox mediator (lithium bromide [LiBr]) to synergistically catalyze electrochemical reactions in Li-O2 batteries. Single-atom cobalt anchored in porous N-doped hollow carbon spheres (CoSAs-NHCS) with high specific surface area and high catalytic activity are utilized as cathode material. However, the potential performances of batteries are difficult to adequately achieve with only CoSAs-NHCS, owing to the blocked electrochemical active sites covered by insulating solid-state discharge product Li2 O2 . Combined with LiBr as redox mediator, the enhanced OER catalytic effect extends throughout all formed Li2 O2 during discharge. Meantime, the certain adsorption effect of CoSAs-NHCS on Br2 and Br3 - can reduce the shuttle of RMox . The synergistic effect of Co single atoms and LiBr can not only promote more Li2 O2 decomposition but also reduce the shuttle effect by absorbing the oxidized redox mediator. Li-O2 batteries with Co single atoms and LiBr achieve ultralow overpotential of 0.69 V and longtime stable cyclability.

Circadian clock protein CRY1 prevents paclitaxel­induced senescence of bladder cancer cells by promoting p53 degradation.

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first­line treatment is cisplatin­based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy­induced senescence can act as a 'back­up' response to chemotherapy in cancer types that are resistant to apoptosis­based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)­induced senescence in cisplatin­resistant bladder cancer cells. Cisplatin­resistant bladder cancer cells were established via long­term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA­ß­Gal staining, but this was not observed in the cisplatin­resistant cells. The cisplatin­resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin­resistant cells, and that CRY1 knockdown restored PTX­induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto­oncogene. These data suggested that the accumulated CRY1 in cisplatin­resistant cells could prevent PTX­induced senescence by promoting p53 degradation.

Does ethnic diversity affect well-being and allostatic load among people across neighbourhoods in England?

Modern societies are facing unprecedented changes in their ethnic composition. Increasing ethnic diversity poses critical new challenges as people interact with new cultures, norms, and values, or avoid such encounters. Heated academic and political debates focus on whether and how changes in ethnic composition affect societies and local communities. Yet, there is insufficient scientific evidence of how living in a more diverse society affects individuals' well-being and health. The aim of this study is to test the extent to which increasing neighbourhood ethnic diversity affects individuals' subjective health and well-being and objective stress levels as measured by allostatic load. We analyse a large panel data set containing over 47,000 English respondents living in 15,545 neighbourhoods in England from the British Household Panel Survey and the UK Household Longitudinal Study, from 2004 to 2011. We match respondents to neighbourhoods and merge contextual information about levels of neighbourhood ethnic diversity and deprivation from UK Censuses, whilst controlling for background characteristics. We distinguish between short- and long-term effects of ethnic diversity on individual subjective well-being and health as well as allostatic load using a set of multilevel mixed-effects models. We make cautious causal interpretations by estimating fixed-effects models and cross-lagged panel models. We assess the robustness of our findings by replicating our analysis using alternative composite measures of diversity and allostatic load. In the short-term, increasing ethnic diversity of local areas is associated with a dip in subjective well-being, but short-term changes are not prolonged or profound enough to affect chronic stress (allostatic load). The initial negative impact of ethnic diversity on subjective well-being and health dissipates with time. In the long-term, no effects of ethnic diversity on well-being and health or chronic stress (allostatic load) are detected. Understanding the dynamic nature of the effects of ethnic diversity on individuals has critical implications for social and public health policies - issues prominent in, for example, the UK (Brexit) and the US (election of President Donald Trump). Our analysis identifies and enables the promotion of beneficial effects, while targeting the pernicious components to turn diversity into a valuable asset in a globalising world.

Resistin Gene Polymorphism Is an Influencing Factor of Postoperative Pain for Chinese Patients.

BACKGROUND: Gene polymorphism is an important factor affecting the efficacy and dosage of opioids. A recent study showed RETN rs3745367 was associated with postoperative pain intensity. OPRM1 gene was confirmed to affect the postoperative analgesic consumption of morphine and other opioids. OBJECTIVE: In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in the RETN, OPRM1 gene and postoperative pain intensity, analgesics consumption, and ADR. The haplotype analysis focus on OPRM1 was also implemented. STUDY DESIGN: This was a prospective, observational study. SETTING: Patients undergoing spinal fusion and correction operation were recruited. Genotypes of rs3745367, rs1799971, rs2075572, and rs9322447 were tested. Pain assessment was performed to measure postoperative pain intensity, postoperative fentanyl and pethidine consumption was recorded to calculate analgesics consumption, and adverse reactions were recorded. METHOD: We recruited 142 patients undergoing spinal correction and fusion. Genotyping was performed by using a real-time polymerase chain reactions (PCRs) system and validated with allelic discrimination assays. The pain was assessed using a numerical rating scale (NRS). Statistical analyses were performed using SPSS software. LD test and the construction and analysis of haplotype were using Haploview software. RESULTS: Rs3745367 demonstrated a significant association with postoperative average pain intensity in 24h (P = 0.015) and 48h (P = 0.001) after surgery. Rs2075572 and rs9322447 influenced postoperative maximal pain intensity in 48h after surgery (P = 0.042, 0.033, respectively). No correlation was found between OPRM1 SNPs and analgesics consumption and adverse reaction. According to the results of this study, a strong LD was observed between rs1799971 and rs9322447 (Block 1, LD parameters: D' = 0.82, r2 = 0.14), rs2075572 and rs9322447 (Block 2, LD parameters: D' = 0.92, r2 = 0.51). LIMITATIONS: The association between rs3745367 with serum resistin levels was not investigated in this research, serum resistin levels of the incision part should be investigated in future studies. CONCLUSION: RETN rs3745367 was associated with postoperative average pain intensity, OPRM1 rs2075572 and rs9322447 may influence postoperative maximal pain intensity.

Guiding Smooth Li Plating and Stripping by a Spherical Island Model for Lithium Metal Anodes.

Lithium metal anodes are considered as promising candidates for next-generation high-energy-density batteries. However, the dendrite formation of Li metal anodes during charge-discharge results in some serious issues. Herein, we show a simple way to flatten the Li metal deposition surface on Ag-modified Cu foil using a spherical island model. In this model, Ag nuclei induce the deposition of Li atoms with low nucleation potentials at the initial heterogeneous nucleation stage. Then, Li homogeneously grows around the spherical islands and these regular islands overlap each other and form a flat Li surface. On the bare Cu foil surface, the Li growth behavior is random, and the deposition surface is porous and covered with dendrites. Stable long-term plating/stripping of a symmetric battery over 800 h at 1 mA cm-2 was achieved. Moreover, the super flat Li structure can be achieved by constructing islands into a three-dimensional (3D) current collector using the spherical island model. Benefiting from the spherical island model, Li||LiFePO4 and Li||O2 batteries with this 3D anode structure can obtain a stable performance.

PXR haplotype clusters will affect the pharmacokinetics of ciclosporin in Chinese renal transplant recipients.

OBJECTIVE: PXR was reported to be the key nuclear receptor regulating the expression of metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of PXR haplotype clusters on ciclosporin concentration in Chinese renal transplant recipients during the early stage after transplantation. METHODS: A total of 98 recipients receiving ciclosporin were genotyped by PCR-RFLP, and the ciclosporin concentration was determined by EMIT. KEY FINDINGS: The frequency of IVS2+55A>G, IVS2+78A>G, IVS6-17C>T, 1792A>G, 1944T>C and 2654T>C variant alleles was 0.343, 0.332, 0.378, 0.515, 0.520 and 0.393, which fitted Hardy-Weinberg equilibrium. Only the IVS6-17C>T and 2654T>C were significantly associated with the ciclosporin C2 /D during the end of the first month. The mean ciclosporin C2 /D level of the PXR*1B haplotype clusters was 1.3-fold and 1.2-fold higher compared with the *1A and *1C. No significant difference was observed in CsA C2 /D between the PXR*1A and PXR*1C. We found no difference in C0 /D among the six genotypes or the three haplotype clusters. CONCLUSIONS: The PXR*1B in Chinese renal transplant patients was associated with ciclosporin concentration. Genetic polymorphisms and specific haplotype clusters in PXR could have significant contributory roles in affecting interethnic variations in drug disposition in the Chinese population.

Magnetic orders and origin of exchange bias in Co clusters embedded oxide nanocomposite films.

Magnetic nanoparticles embedded oxide semiconductors are interesting candidates for spintronics in view of combining ferromagnetic (FM) and semiconducting properties. In this work, Co-ZnO and Co-V2O3 nanocomposite thin films are synthesized by Co ion implantation in crystalline thin films. Magnetic orders vary with the implantation fluence in Co-ZnO, where superparamagnetic (SPM) order appears in the low-fluence films (2 × 1016 and 4 × 1016 ions cm-2) and FM order co-exists with the SPM phase in high-fluence films (1 × 1017 ions cm-2). Exchange bias (EB) appears in the high-fluence films, with an EB field of about 100 Oe at 2 K and a blocking temperature of around 100 K. On the other hand, Co-V2O3 thin films with an implantation fluence of 3.5 × 1016 ions cm-2 exhibit a clear antiferromagnetic (AFM) coupling at low temperatures without the EB effect. The different magnetic behavior of the Co-implanted films with different Co content leads us to conclude that the observed EB effect in the Co-ZnO films results from the FM/AFM coupling between sizable Co nanoparticles and their CoO/Co3O4 surroundings in the (Zn,Co)O matrix. On the other hand, the absence of EB effect in Co-V2O3 appears to be due to the small size of the FM Co nanoparticles in spite of an AFM magnetic order. Detailed studies of magnetic orders and EB effect in magnetic nanocomposite semiconductors can pave the way for their application in spintronics.

Oxygen-Induced Bi5+-Self-Doped Bi4V2O11 with a p-n Homojunction Toward Promoting the Photocatalytic Performance.

Bi5+-self-doped Bi4V2O11 (Bi5+-BVO) nanotubes with p-n homojunctions are fabricated via an oxygen-induced strategy. Calcinating the as-spun fibers with abundant oxygen plays a pivotal role in achieving Bi5+ self-doping. Density functional theory calculations and experimental results indicate that Bi5+ self-doping can narrow the band gap of Bi4V2O11, which contributes to enhancing light harvesting. Moreover, Bi5+ self-doping endows Bi4V2O11 with n- and p-type semiconductor characteristics simultaneously, resulting in the construction of p-n homojunctions for retarding rapid electron-hole recombination. Benefiting from these favorable properties, Bi5+-BVO exhibits a superior photocatalytic performance in contrast to that of pristine Bi4V2O11. Furthermore, this is the first report describing the achievement of p-n homojunctions through self-doping, which gives full play to the advantages of self-doping.

Co-Rich ZnCoO Nanoparticles Embedded in Wurtzite Zn1-xCoxO Thin Films: Possible Origin of Superconductivity.

Co-rich ZnCoO nanoparticles embedded in wurtzite Zn0.7Co0.3O thin films are grown by pulsed laser deposition on a Si substrate. Local superconductivity with an onset Tc at 5.9 K is demonstrated in the hybrid system. The unexpected superconductivity probably results from Co3+ in the Co-rich ZnCoO nanoparticles or from the interface between the Co-rich nanoparticles and the Zn0.7Co0.3O matrix.

CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients.

OBJECTIVE: Both cyclosporine and tacrolimus display a narrow therapeutic index as well as high interindividual pharmacokinetic variability. We approached the effect of the CYP3A4*18B and CYP3A5*3 polymorphisms and haplotypes on the whole blood cyclosporine or tacrolimus concentration in Chinese renal transplant patients during the first month after transplantation. MATERIALS AND METHODS: A total of 83 recipients receiving tacrolimus or cyclosporine was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The whole blood concentration was measured by enzyme-multiplied immunoassay technique. RESULTS: Both CYP3A4*18B and CYP3A5*3 polymorphisms affected the tacrolimus dose-adjusted trough concentration (C0/D). The tacrolimus C0/D was higher in carriers of haplotype GG compared with the non-carriers. The cyclosporine dose-adjusted 2-hour post-dose concentrations (C2/D), dose-adjusted C0 + C2 ((C0 + C2)/D) and C2/C0 during Days 15 - 21 displayed significant difference among the three genotypes. Statistical difference was observed between CYP3A4*1/*1 and CYP3A4*18B/*18B groups and between CYP3A4*1/*18B and CYP3A4*18B/*18B groups, but no difference was detected between CYP3A4*1/*1 and CYP3A4*1/*18B groups. No difference was found in C0/D among the three genotypes of CYP3A4*18B polymorphism, and neither CYP3A5*3 polymorphisms nor CYP3A haplotype-derived genotypes affected the cyclosporine dose-adjusted concentration. CONCLUSIONS: Genetic polymorphisms of CYP3A5*3 and CYP3A4*18B may be partly responsible in large interindividual variability of cyclosporine and tacrolimus blood levels in Chinese renal transplant patients during the first month after transplantation. A patient carried combined genotype of CYP3A4*1/*1-CYP3A5* 3/*3 might require lower tacrolimus doses to achieve target concentration levels. Genotyping of CYP3A4*18B and CYP3A5*3 before transplantation is of benefit in determining a suitable initial dose for each patient.