Stacking Transformation-Triggered Circularly Polarized Luminescence Reversion in γ-Cyclodextrins-Pyrene Co-assembly.

​Considerable attention has been directed towards cyclodextrins (CDs) in the creation of co-assembled CPL-active materials, owing to their intrinsic chiral host cavities and synergistic host-guest interactions. However, achieving reversed CPL emission regulation with single-handedness CDs moiety poses a significant challenge. In this study, we have devised a series of γ-CD-based host-guest complexes comprising dual pyrene imidazolium derivatives with multiple linkers, which exhibit reversed circularly polarized emission. We have uncovered that the transformation of excimer stacking within γ-CD/pyrene complexes contributes to the inverted CPL emissions originating from a single-handed chiral host. This research elucidates the phenomenom of (+)- and (-)-circularly polarized excimer emission (CPEE) within γ-CD, arising from right- and left-handed stacking conformations, respectively.

Goiter in the Qing Dynasty.

Empress Dowager Cixi, the supreme ruler of China's Qing Dynasty, along with Imperial Concubine Jin, may have suffered from goiter. Our suspicions were aroused by two interesting historical photographs. Herein, we provide a medical interpretation of these historical images in an attempt to present the cases of these two historical figures.

Research on parameterized modeling and mechanical characteristics of shearer cables.

Shearer cables, subjected to large deformations and exposed to harsh working conditions during frequent back-and-forth movements, pose difficulties in achieving comprehensive mechanical performance and extended fatigue life. This study addresses parametric modeling challenges related to determining tangency within and between layers, recursively generating spiral curves from the (n-1)-th level to the n-th level, and constructing irregular surfaces for insulation and sheath. Investigating tensile and bending properties, the research explores the impact of varying pitch diameter ratios at different stranding levels, stranding directions, and monofilaments on mechanical performance across scales. The results reveal a nonlinear increase in stress in power and control conductors with growing pitch diameter ratios. The optimal combination is determined as a pitch diameter ratio of 6 for cabling, 5 for the control conductor, and 14 for the power conductor. The predicted fatigue life of the improved cable by Ncode aligns with bending test results, demonstrating functionality up to 15.12e4 cycles. Stress distribution in parallel stranding is lower and more even, tending to scatter. Conversely, counter stranding experiences relatively higher stress, ensuring a more stable structure. While maintaining a constant effective conductor cross-sectional area, finer monofilaments result in higher cross-sectional filling ratios, enhancing tensile and bending performance.

The dCas9-based genome editing in Plasmodium yoelii.

Genetic editing is a powerful tool for functional characterization of genes in various organisms. With its simplicity and specificity, the CRISPR-Cas9 technology has become a popular editing tool, which introduces site-specific DNA double-strand breaks (DSBs), and then leverages the endogenous repair pathway for DSB repair via homology-directed repair (HDR) or the more error-prone non-homologous end joining (NHEJ) pathways. However, in the Plasmodium parasites, the lack of a typical NHEJ pathway selects for DSB repair through the HDR pathway when a homologous DNA template is available. The AT-rich nature of the Plasmodium genome exacerbates this drawback by making it difficult to clone longer homologous repair DNA templates. To circumvent these challenges, we adopted the hybrid catalytically inactive Cas9 (dCas9)-microbial single-stranded annealing proteins (SSAP) editor to the Plasmodium genome. In Plasmodium yoelii, we demonstrated the use of the dCas9-SSAP, as the cleavage-free gene editor, by targeted gene deletion and gene tagging, even using shorter homologous DNA templates. This dCas9-SSAP method with a shorter DNA template, which did not require DSBs, independent of HDR and NHEJ, would be a great addition to the existing genetic toolbox and could be deployed for the functional characterization of genes in Plasmodium, contributing to improving the ability of the malaria research community in characterizing more than half of genes with unknown functions.IMPORTANCEMalaria caused by Plasmodium parasites infection remains a serious threat to human health, with an estimated 249 million malaria cases and 608,000 deaths worldwide in 2022, according to the latest report from the World Health Organization (WHO). Here, we demonstrated the use of dCas9-single-stranded annealing protein, as the cleavage-free gene editor in Plasmodium yoelii, by targeted deletion and gene tagging, even using shorter homologous DNA templates. This method with a shorter DNA template, which did not require DSBs, independent of HDR and NHEJ, showing the potential significance in greatly improving our ability to elucidate gene functions, would contribute to assisting the malaria research community in deciphering more than half of genes with unknown functions to identify new drug and vaccine targets.

Validation of the RBP-9801 oscillometric blood pressure monitor in the general population according to the association for the Advancement of Medical Instrumentation/European Society of Hypertension/ International Organization for Standardization Universal Standard.

The aim of this study was to evaluate the accuracy of the single upper-arm cuff oscillometric blood pressure (BP) monitor RBP-9801 developed for office and home BP measurement in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. A total of 105 subjects were recruited and 85 were analyzed. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.3 ± 6.4/3.1 ± 5.8 mmHg (systolic/diastolic). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 5.24/5.03 mmHg (systolic/diastolic). The conclusion is that the RBP-9801 oscillometric device for office and home BP measurement fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in the general population and can be recommended for clinic and self-use at home.

Validation of the Raycome model M2 ambulatory blood pressure monitor in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard (ISO 81060-2:2018).

OBJECTIVE: The aim of this study was to evaluate the accuracy of the Raycome model M2 oscillometric upper-arm blood pressure (BP) monitor developed for ambulatory BP measurement in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) at rest and during dynamic exercise. METHOD: Subjects were recruited to fulfill the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in the general population using the same arm sequential BP measurement method. Three cuffs of the test device were used for arm circumference 18-22 cm (small), 22-32 cm (medium) and 32-42 cm (large). RESULTS: For the general validation study, 106 subjects were recruited and 85 were analyzed. For validation criterion 1, the mean ±â€…SD of the differences between the test device and reference BP readings was 0.5 ±â€…6.2/-0.2 ±â€…5.1 mmHg (systolic/diastolic). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 5.23/4.50 mmHg (systolic/diastolic). In the ambulatory validation study ( N  = 35), the mean difference was 0.4 ±â€…5.9/-1.1 ±â€…5.8 mmHg. The Raycome model M2 performed well against the standard in both the general and ambulatory validations and the Bland-Altman plots did not show any systematic variation in the error. CONCLUSION: These data show that the Raycome model M2 monitor meets the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) and in the ambulatory setting, indicating its suitability for measuring BP in the general population.

Engineering lentivirus envelope VSV-G for liver targeted delivery of IDOL-shRNA to ameliorate hypercholesterolemia and atherosclerosis.

Lentiviral vectors (LVs) have been widely used as a tool for gene therapies. However, tissue-selective transduction after systemic delivery remains a challenge. Inducible degrader of low-density lipoprotein receptor is an attractive target for treating hypercholesterolemia. Here, a liver-targeted LV, CS8-LV-shIDOL, is developed by incorporating a hepatocyte-targeted peptide derived from circumsporozoite protein (CSP) into the lentivirus envelope for liver-targeted delivery of IDOL-shRNA (short hairpin RNA) to alleviate hypercholesterolemia. Tail-vein injection of CS8-LV-shIDOL results in extremely high accumulation in liver and nearly undetectable levels in other organs in mice. In addition, it shows superior therapeutic efficacy in lowering serum low-density lipoprotein cholesterol (LDL-C) and reducing atherosclerotic lesions over unmodified LV-shIDOL in hyperlipidemic mice. Mechanically, the envelope-engineered CS8-LV-shIDOL can enter liver cells via low-density lipoprotein receptor-related protein (LRP). Thus, this study provides a novel approach for liver-targeted delivery of IDOL-shRNA to treat hypercholesterolemia by using an envelope-engineered LV, and this delivery system has great potential for liver-targeted transgene therapy.

Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage.

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-µmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 µmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Associations of personal PM2.5-bound heavy metals and heavy metal mixture with lung function: Results from a panel study in Chinese urban residents.

BACKGROUND: There are a few reports on the associations between fine particulate matter (PM2.5)-bound heavy metals and lung function. OBJECTIVES: To evaluate the associations of single and mixed PM2.5-bound heavy metals with lung function. METHODS: This study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM2.5-bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM2.5-adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM2.5-bound heavy metal mixtures and lung function. RESULTS: In the single exposure analyses, significant negative associations of PM2.5-bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM2.5-bound heavy metal mixture. The BKMR models suggested negative associations of PM2.5-bound lead and antimony with lung function. In addition, PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM2.5-bound lead, manganese, and vanadium, and increased with the elevated PM2.5-bound copper. CONCLUSIONS: The negative relationships were detected between PM2.5-bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM2.5-bound heavy metal mixture, PM2.5-bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75.

Intrinsically Safe Lithium Metal Batteries Enabled by Thermo-Electrochemical Compatible In Situ Polymerized Solid-State Electrolytes.

In situ polymerized solid-state electrolytes have attracted much attention due to high Li-ion conductivity, conformal interface contact, and low interface resistance, but are plagued by lithium dendrite, interface degradation, and inferior thermal stability, which thereby leads to limited lifespan and severe safety hazards for high-energy lithium metal batteries (LMBs). Herein, an in situ polymerized electrolyte is proposed by copolymerization of 1,3-dioxolane with 1,3,5-tri glycidyl isocyanurate (TGIC) as a cross-linking agent, which realizes a synergy of battery thermal safety and interface compatibility with Li anode. Functional TGIC enhances the electrolyte polymeric level. The unique carbon-formation mechanism facilitates flame retardancy and eliminates the battery fire risk. In the meantime, TGIC-derived inorganic-rich interphase inhibits interface side reactions and promotes uniform Li plating. Intrinsically safe LMBs with nonflammability and outstanding electrochemical performances under extreme temperatures (130 °C) are achieved. This functional polymer design shows a promising prospect for the development of safe LMBs.

Rapid Discriminative Identification of the Two Predominant Echinococcus Species from Canine Fecal Samples in the Tibetan Region of China by Loop-Mediated Isothermal Amplification-Lateral Flow Dipstick Assay.

Echinococcosis poses a significant concern in the fields of public health and veterinary care as it can be transmitted between animals and humans. The primary endemic subtypes are cystic echinococcosis (CE) and alveolar echinococcosis (AE), which result from infestation by Echinococcus granulosus and Echinococcus multilocularis, respectively. A prominent epidemic of echinococcosis greatly affects the Tibet Autonomous Region (TAR) in China. A new technique called the loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) test is introduced in this research to differentiate between E. granulosus and E. multilocularis using their repetitive genetic sequences. The test is characterized by its portable nature, simple operation, quick result production, high sensitivity, and low susceptibility to aerosol contamination. The LAMP-LFD method demonstrated an exceptional minimal detection limit, reaching levels as low as approximately 1 fg/µL (femtogram per microliter) of genomic DNA. The assay's specificity was assessed, and no cross-reactivity was seen. A total of 982 dog fecal samples were collected from 54 counties in the TAR region between July 2021 and June 2022. The established method underwent validation using a commercially available ELISA kit. The agreement rate between the LAMP-LFD and ELISA methods was 97.25%, with a sensitivity of 96.05% and a specificity of 97.35%. The assay described in this study improves specificity by using a double-labeled probe, and it reduces the risk of false-positive results caused by aerosol contamination through the use of a sealed device. This makes it a suitable choice for quickly and accurately identifying the two main types of Echinococcus in field settings.