A cost-effective smartphone-based device for rapid C-reaction protein (CRP) detection using magnetoelastic immunosensor.

C-Reaction protein (CRP) is a marker of nonspecific immunity for vital signs and wound assessment, and it can be used to diagnose infections in clinical medicine. However, measuring CRP level currently requires hospital-based instruments, high-cost reagents, and a complex process, all of which have limited its full capabilities for self-detection, a growing trend in modern medicine. In this study, we developed a novel smartphone-based device using advanced methods of magnetoelastic immunosensing to mitigate these limitations. We combined a system-on-chip (SoC) hardware architecture with smartphone apps to realize the sampling of resonance frequency shift on magnetoelastic chips, which can determine the ultra-sensitivity to mass change caused by the binding of anti-CRP antibody and CRP. Through detecting a multi-group of samples, we found that the resonance frequency shift was linearly proportional to the CRP concentration in the range from 0.1 to 100 µg mL-1, with a sensitivity of 12.90 Hz µg-1 mL-1 and a detection limit of 2.349 × 10-4 µg mL-1. Meanwhile, compared with the large-scale instrument used in clinical settings, the performance of our device was stable and significantly more portable, rapid and cost-effective, offering excellent potential for modern home-based diagnosis.

Risk stratification of acute myeloid leukemia: Assessment using a novel prediction model based on ferroptosis-immune related genes.

In acute myeloid leukemia (AML), the link between ferroptosis and the immune microenvironment has profound clinical significance. The objective of this study was to investigate the role of ferroptosis-immune related genes (FIRGs) in predicting the prognosis and therapeutic sensitivity in patients with AML. Using The Cancer Genome Atlas dataset, single sample gene set enrichment analysis was performed to calculate the ferroptosis score of AML samples. To search for FIRGs, differentially expressed genes between the high- and low-ferroptosis score groups were identified and then cross-screened with immune related genes. Univariate Cox and LASSO regression analyses were performed on the FIRGs to establish a prognostic risk score model with five signature FIRGs (BMP2, CCL3, EBI3, ELANE, and S100A6). The prognostic risk score model was then used to divide the patients into high- and low-risk groups. For external validation, two Gene Expression Omnibus cohorts were employed. Overall survival was poorer in the high-risk group than in the low-risk group. The novel risk score model was an independent prognostic factor for overall survival in patients with AML. Infiltrating immune cells were also linked to high-risk scores. Treatment targeting programmed cell death protein 1 may be more effective in high-risk patients. This FIRG-based prognostic risk model may aid in optimizing prognostic risk stratification and treatment of AML.

Epidemiological trends of urinary tract infections, urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019.

BACKGROUND: Urinary tract infections (UTI), urolithiasis, and benign prostatic hyperplasia (BPH) are three of the most common nonmalignant conditions in urology. However, there is still a lack of comprehensive and updated epidemiological data. This study aimed to investigate the disease burden of UTI, urolithiasis, and BPH in 203 countries and territories from 1990 to 2019. METHODS: Data were extracted from the Global Burden of Disease 2019, including incident cases, deaths, disability-adjusted life-years (DALYs) and corresponding age-standardized rate (ASR) from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to evaluate the trends of ASR. The associations between disease burden and social development degrees were analyzed using a sociodemographic index (SDI). RESULTS: Compared with 1990, the incident cases of UTI, urolithiasis, and BPH increased by 60.40%, 48.57%, and 105.70% in 2019, respectively. The age-standardized incidence rate (ASIR) of UTI increased (EAPC = 0.08), while urolithiasis (EAPC = - 0.83) and BPH (EAPC = - 0.03) decreased from 1990 to 2019. In 2019, the age-standardized mortality rate (ASMR) of UTI and urolithiasis were 3.13/100,000 and 0.17/100,000, respectively. BPH had the largest increase (110.56%) in DALYs in the past three decades, followed by UTI (68.89%) and urolithiasis (16.95%). The burden of UTI was mainly concentrated in South Asia and Tropical Latin America, while the burden of urolithiasis and BPH was recorded in Asia and Eastern Europe. Moreover, the ASIR and SDI of urolithiasis in high-SDI regions from 1990 to 2019 were negatively correlated, while the opposite trend was seen in low-SDI regions. In 2019, the ASIR of UTI in females was 3.59 times that of males, while the ASIR of urolithiasis in males was 1.96 times higher than that in females. The incidence was highest in the 30-34, 55-59, and 65-69 age groups among the UTI, urolithiasis, and BPH groups, respectively. CONCLUSION: Over the past three decades, the disease burden has increased for UTI but decreased for urolithiasis and BPH. The allocation of medical resources should be based more on the epidemiological characteristics and geographical distribution of diseases.

Large-scale genomic analysis reveals the genetic cost of chicken domestication.

BACKGROUND: Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication. RESULTS: We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the "cost of domestication" hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes. CONCLUSION: This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.

N-Substituted Phenothiazines as Environmentally Friendly Hole-Transporting Materials for Low-Cost and Highly Stable Halide Perovskite Solar Cells.

Most of the high-performing halide perovskite solar cells (PSCs) leverage toxic chlorinated solvents (e.g., o-dichlorobenzene or chlorobenzene) for the hole-transporting material (HTM) processing and/or antisolvents in the perovskite film fabrication. To minimize the environmental and health-related hazards, it is highly desirable, yet at the same time demanding, to develop HTMs and perovskite deposition processes relying on nonhalogenated solvents. In this work, we designed two small molecules, AZO-III and AZO-IV, and synthesized them via simple and environmentally friendly Schiff base chemistry, by condensation of electron-donating triarylamine and phenothiazine moieties connected through an azomethine bridge. The molecules are implemented as HTMs in PSCs upon processing in a nonchlorinated (toluene) solvent, rendering their synthesis and film preparation eco-friendly. The enhancement in the power conversion efficiency (PCE) was achieved when switching from AZO-III (9.77%) to AZO-IV (11.62%), in which the thioethyl group is introduced in the 2-position of the phenothiazine ring. Additionally, unencapsulated PSCs based on AZO-III displayed excellent stabilities (75% of the initial PCEs is retained after 6 months of air exposure for AZO-III to be compared with a 48% decrease of the initial PCE for Spiro-OMeTAD-based devices). The outstanding stability and the extremely low production cost (AZO-III = 9.23 $/g and AZO-IV = 9.03 $/g), together with the environmentally friendly synthesis, purification, and processing, make these materials attractive candidates as HTMs for cost-effective, stable, and eco-friendly PSCs.

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations.

OBJECTIVE: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. RESULTS: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. CONCLUSION: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.

Assessment of tolerance to multistresses and in vitro cell adhesion in genetically modified Lactobacillus plantarum 590.

Lactobacillus plantarum (Lp) is a lactic acid bacterium that has many excellent traits that meet the needs of industrial production. Genetically modified (GM) Lp590 was obtained from Lp that was modified by the insertion of the gene nisI, which can confer resistance to nisin and play a role as a bio-preservative. Here, explorations were made to assess the safety of GM Lp590 and establish an in vitro evaluation model. The ability of Lp590 to tolerate both environmental stresses (such as temperatures ranging from 52 to 4 °C, or exposure to ethanol, oxygen, and osmotic stresses) and gastrointestinal transit was assessed. Lp590 showed a tolerance to 4 °C and ethanol (20%) within a period of 240 min that was similar to Lp. Notably, Lp590 can tolerate higher temperature (52 °C) and higher levels of H(2)O(2) (2%) and NaCl (4.0 M) than Lp. In contrast, Lp590 has the same gastrointestinal transit tolerance as Lp. In addition, Lp590 can adhere to Caco-2 cells, and it has no adverse effect on the cell membrane in vitro. These results indicate that GM Lp590 has many desirable biological characteristics and has good prospects for industrial applications. A useful and comprehensive exploration has been undertaken to establish a new in vitro evaluation model for genetically modified microorganisms (GMMs).

Who donates blood at five ethnically and geographically diverse blood centers in China in 2008.

BACKGROUND: In China recruitment and retention of sufficient numbers of safe blood donors continues to be a challenge. Understanding who donates blood, particularly those who donate larger (>200 mL) whole blood (WB) units, will help blood centers to target more effective recruitment and retention strategies. STUDY DESIGN AND METHODS: Demographic characteristics of 226,489 allogeneic WB donors from January to December 2008 at five geographically and ethnically diverse, urban blood centers were analyzed. RESULTS: The typical Chinese WB donor can be characterized as first-time volunteer (67.9%), male (56.9%), less than 45 years old (93.8%), and Han ethnicity (86.1%). Most donors had some college or below educational level (77.5%), donated at a mobile collection site (97.6%), and donated 300- or 400-mL units (76.0%). Differences in WB volume donations and donor demographics exist among the five centers. CONCLUSION: In China compared to the United States, donations are made by younger donors and donors give infrequently and make smaller WB donations. To help ensure supply adequacy, continued efforts are needed to have donors give larger volumes of WB in China.

International Bureau for Epilepsy survey of children, teenagers, and young people with epilepsy: data in China.

The goals of this study were to assess the perception of people with or directly involved with childhood and adolescent epilepsy in China, and to gain insight into the real-life effects that epilepsy can have on quality of life, development, and opportunities for the future. Survey questionnaires were developed by the International Bureau for Epilepsy for three groups: teenagers and young adults, parents/caregivers of children with epilepsy, and health care professionals. In total we received 968 responses from 20 cities in China. Nearly two-thirds of teenagers and young adults with epilepsy (64.9%) and two-thirds of parents/caregivers of children with epilepsy (64.0%) who responded to the survey had kept epilepsy a secret from others. When asked specifically about drug-related side effects, more than half of teenagers and young adults with epilepsy reported experiencing side effects, specifically dizziness (23.9%), weight change (22.9%), and headache (14.5%). Health care professionals reported cognitive side effects (94.2%), mood change (56.7%), and skin rash (50%) in their patients with epilepsy. More than two-thirds of the teenagers and young adults with epilepsy (75.7%) expected the condition to hinder their lives in the future, affecting their chances of getting a job (52.6%), continuing their education (35.5%), and getting a boyfriend or girlfriend (33.7%). Among parents/caregivers of children with epilepsy, 85.7% expected the condition to hinder their child's life in the future. This survey documents some of the real-life consequences of epilepsy and highlights the important challenges and issues faced by people with epilepsy and their families in China. Ensuring that people are as free from seizures as possible and minimizing the side effects of treatment must be the primary goals of epilepsy management.

Safety assessment of Cry1Ab/Ac fusion protein.

Cry1ab/ac gene was fused by both the cry1ab gene (GenBank Accession No. X54939) and the cry1ac gene (GenBank Accession No. Y09787), which was widely used in genetically modified (GM) rice, cotton, maize and so on. In order to support the safety assessment of GM food or feed products containing Cry1Ab/Ac protein, sufficient quantities of Cry1Ab/Ac protein were produced in Escherichia coli for in vitro evaluation and animal studies. The Cry1Ab/Ac protein does not possess the characteristics associated with food toxins or allergens, i.e., it has no sequence homology with any known allergens or toxins, and no N-glycosylation sites, can be rapidly degraded in gastric and intestinal fluids, and is devoid of adverse effects in mice by gavage at a high dose level of 5g (Cry1Ab/Ac protein)/kg body weight. In conclusion, there is a reasonable certainty of no harm resulting from the inclusion of the Cry1Ab/Ac protein in human food or animal feed.