Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Characteristics and risk assessment of heavy metals in groundwater at a typical smelter-contaminated site in Southwest China.

To explore the characteristics and evaluate the risk of heavy metals in groundwater at a typical smelter-contaminated site, this study focuses on a representative a historical arsenic smelting plant in Southwest China, where the primary historical products were metallic arsenic (∼1000 tons/year) and arsenic trioxide (∼2000 ton/year). The results demonstrated As and Pb as the main pollutants in soil, and As and Cd as main pollutants in groundwater through soil profiling and quarterly groundwater analysis. The maximum As and Pb in the surface soil were 76800 and 2290 mg/kg, respectively, with As vertically infiltrating the deep gravel-sand layer (18-20 m). The groundwater pollution distribution progressively increased along flow direction, influenced by seasonal surface runoff and infiltration fluctuations. The groundwater pollutant concentrations during the dry season notably surpassed those during the wet season, with maximum As and Cd concentrations of 111.64 mg/L and 19.85 µg/L during the dry season, respectively. Furthermore, the analytic hierarchy process (AHP) was applied to evaluate the comprehensive risk of contaminated-site across pollution source load, regional groundwater intrinsic vulnerability, and evaluation of nearby sensitive receptors. The results revealed that the carcinogenic risk of lead in surface soil was moderate to high, while arsenic posed a high carcinogenic risk, contributing to an overall carcinogenic risk proportion of 89.6% in surface soil. Exposure through groundwater intake was identified as the primary pathway, with carcinogenic and noncarcinogenic risks exceeding those through skin contact. The final weights result demonstrated that the principal risk factors are the intrinsic arsenic load and protective target characteristics of regional groundwater at this site. This study provides a reference for comprehensive assessments of similarly contaminated industrial and smelting sites.

Optimized production of full-length PCV2d virus-like particles in Escherichia coli: A cost-effective and high-yield approach for potential vaccine antigen development.

Porcine circovirus type 2 (PCV2) is a globally prevalent infectious pathogen affecting swine, with its capsid protein (Cap) being the sole structural protein critical for vaccine development. Prior research has demonstrated that PCV2 Cap proteins produced in Escherichia coli (E. coli) can form virus-like particles (VLPs) in vitro, and nuclear localization signal peptides (NLS) play a pivotal role in stabilizing PCV2 VLPs. Recently, PCV2d has emerged as an important strain within the PCV2 epidemic. In this study, we systematically optimized the PCV2d Cap protein and successfully produced intact PCV2d VLPs containing NLS using E. coli. The recombinant PCV2d Cap protein was purified through affinity chromatography, yielding 7.5 mg of recombinant protein per 100 ml of bacterial culture. We augmented the conventional buffer system with various substances such as arginine, ß-mercaptoethanol, glycerol, polyethylene glycol, and glutathione to promote VLP assembly. The recombinant PCV2d Cap self-assembled into VLPs approximately 20 nm in diameter, featuring uniform distribution and exceptional stability in the optimized buffer. We developed the vaccine and immunized pigs and mice, evaluating the immunogenicity of the PCV2d VLPs vaccine by measuring PCV2-IgG, IL-4, TNF-α, and IFN-γ levels, comparing them to commercial vaccines utilizing truncated PCV2 Cap antigens. The HE staining and immunohistochemical tests confirmed that the PCV2 VLPs vaccine offered robust protection. The results revealed that animals vaccinated with the PCV2d VLPs vaccine exhibited high levels of PCV2 antibodies, with TNF-α and IFN-γ levels rapidly increasing at 14 days post-immunization, which were higher than those observed in commercially available vaccines, particularly in the mouse trial. This could be due to the fact that full-length Cap proteins can assemble into more stable PCV2d VLPs in the assembling buffer. In conclusion, our produced PCV2d VLPs vaccine elicited stronger immune responses in pigs and mice compared to commercial vaccines. The PCV2d VLPs from this study serve as an excellent candidate vaccine antigen, providing insights for PCV2d vaccine research.

Impact of long-term care insurance on health inequality in older adults in China based on the concentration index approach.

BACKGROUND: Several studies have shown that social security would reduce health inequalities. However, little was known about the relationship between long-term care insurance and health inequality. We aimed to evaluate the impact of long-term care insurance on health status and health inequality in older adults using a nationally representative cohort. METHODS: Based on four waves of data from the China Health and Retirement Longitudinal Study (CHARLS 2011, 2013, 2015 and 2018), we used the staggered difference in difference (DID) design with the order probit regression models and the concentration index approach as well as decomposition analysis to assess the contribution of long-term care insurance towards residents' health status and health inequality in older adults aged ≥65 y. We further used the semi-parametric DID model for robustness testing. RESULTS: Long-term care insurance demonstrated its role, improving self-assessed health in the study population (ßcoefficient: 0.090, 95% CI 0.087 to 0.092, p<0.001). The estimation results of the semi-parametric DID were consistent with those of the staggered DID. The income-related health concentration index was 0.0005, having a contribution rate of 1.639% to health inequality in older adults. Decomposition analysis revealed that different policies and residential areas were more influential on the observed health inequalities. CONCLUSIONS: The findings implied that long-term care insurance has widened the health inequality while improving health status in older adults. Additional investment in more comprehensive insurance coverage and increased accessibility to enhance implementation of long-term care insurance is warranted to close the gap.

Associations between tea-drinking habits and health-related quality of life in Chinese adults: a mediation analysis based on sleep quality.

BACKGROUND: The aim of this study was to explore the association between tea-drinking habits and health-related quality of life (HRQoL) in Chinese adults and the mediating effect of sleep quality in this association. METHODS: Data were derived from the 2020 Survey of Social Factors for Chronic Disease Prevention and Control among adults in Lishui District, Nanjing, Jiangsu Province, China. Tea-drinking habits were measured by participants' self-report. The HRQoL was measured using the 12-item Short Form Health Survey. Multiple linear regression modelling and mediating effects modelling were used for analyses. RESULTS: Habitual tea drinking, frequent tea drinking (drinking tea 6-7 days per week), tea concentration and <10 g of tea per day were strongly associated with an increase in HRQoL among Chinese adults (all p<0.05). The association between tea-drinking habits and HRQoL among Chinese adults was more pronounced in the male population and in those ≥45 y of age (all p<0.05). Tea drinking habits may improve HRQoL in Chinese adults by enhancing sleep quality (all p<0.05). CONCLUSIONS: Maintaining the habit of habitual tea drinking (6-7 days per week), in small amounts (<10 g tea per day) was conducive to improving HRQoL of Chinese adults by improving sleep quality.

Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor.

Background: For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. Objectives: We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Methods: Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan-Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). Conclusion: The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice.

A signal quality assessment method for fetal QRS complexes detection.

OBJECTIVE: Non-invasive fetal ECG (NI-FECG) provides a non-invasive method to monitor the health of the fetus. However, the NI-FECG is easily interfered by noise, which makes the signal quality decline, leading to the fetal heart rate (FHR) monitoring becoming a challenging task. METHODS: In this work, an algorithm for dynamic evaluation of signal quality is proposed to improve the multi-channel FHR monitoring. The innovation of the method is to assess the signal quality in the process of multi-channel fetal QRS (FQRS) complexes detection. Specifically, the detected FQRS is used as quality unit. Each quality unit can be a true R peak (TR) or a false R peak (FR). It is the basic quality information in this work. The signal quality of each channel is estimated by estimating the correctness of the detection results. Further, the TRs of all channels can be fused to obtain more reliable fetal heart rate monitoring. MAIN RESULTS: Analysis results demonstrate that the proposed algorithm is capable of selecting the good quality signal for FQRS detection achieving 97.40% PPV, 98.33% SE and 97.86% F1. SIGNIFICANCE: This work sheds light on the quality assessment of fetal monitoring signal.

Cost-sharing reduction and health service utilisation, health-related lifestyles, and obesity: evidence from the Australian health concession card policy.

BACKGROUND: The Australian Health Concession Card (HCC) policy aims to improve access to affordable health services and medicines by providing reduced patient cost-sharing. This study explored the association between HCC holding and health service utilisation, as well as health-related lifestyles and obesity in Australian adults. METHODS: The Australian National Health Survey data were used to derive three sets of study outcomes. Multivariable generalised linear regression models were used to estimate the association between concessional status and study outcomes after controlling for socio-demographic factors. RESULTS: HCC holders, compared to their non-concessional counterparts, had more visits to GPs (1.01, 95% CI: 0.74-1.30), specialists (0.23, 95% CI: 0.02-0.44), outpatient clinics (0.19, 95% CI: 0.06-0.31), and had more hospital admissions (0.04, 95% CI: -0.05-0.91). There was no significant difference in visits to doctors and health professionals about mental health problems among HCC holders and their counterparts. Moreover, less HCC holders consumed alcohol on ≥3days a week (OR: 0.75, 95% CI: 0.59-0.93) and had less of an alcohol risk that exceeded the 2001 alcohol guidelines (0.83, 95% CI: 0.69-0.99). CONCLUSIONS: This study revealed evidence that reduced patientcost-sharing provided by HCC policy was positively correlated with more health service utilisation after adjusting for socio-demographic characteristics. Strategies to prioritise resources are necessary.

Global morbidity and mortality of lower respiratory infections: A population -based study.

BACKGROUND: This study provides a comprehensive, comparative and updated estimates of temporal patterns of lower respiratory infections (LRIs) globally over the past three decades. METHODS: The data on morbidity and mortality of patients with LRIs at the global, regional and national levels were retrieved from the Global Burden of Disease (GBD) 2019 study. RESULTS: Globally, the incident cases of LRIs increased from 414,342,866 [95% uncertainty interval (UI):383,529,625 to 449, 086,938]in 1990 to 488,902,504(95% UI: 457,572,987 to 522,635,542)in 2019 with the age standardized incidence rate (ASIR) decreased from 8,276/100,000 persons (95% UI: 7,727 to 8,892) to 6,295/100,000 persons (95% UI: 5,887 to 6,737) between 1990 and 2019. Number of LRIs deaths were 2,493,200 (95% UI: 2,268,184 to 2,736,184) in 2019, a decrease of 24.9% (95% UI: -34.4 to -15.4) in the past 30 years. Meanwhile, the age-standardized death rate (ASDR) declined also from 67/100,000 persons (95% UI: 61 to 73) in 1990 to 34/100,000 persons (95% UI: 31 to 38) in 2019. Moreover, the numbers and age-standardized rates per 100,000 persons of morbidity and mortality varied widely by age, sex, Socio-Demographic Index (SDI) quintiles, and geographical locations in 2019. CONCLUSION: LRIs remain a major public health concern . Some differences in age, sex, SDI quintiles, and geographical locations contribute to LRIs-related global health policy development and health system resource optimization.

Association of sensory impairment with healthcare use and costs among middle-aged and older adults in China.

OBJECTIVES: This study aimed to explore the association of visual, hearing, or dual sensory impairment with healthcare use and costs. STUDY DESIGN: This is a cohort study. METHODS: These research data were from the China Health and Retirement Longitudinal Study spanning 2011-2018 and included 8982 community-dwelling middle-aged and older adults (aged ≥45 years at baseline). Sensory impairment was measured according to self-reported assessment of visual and hearing functions, and healthcare use and costs were ascertained via self-report. The associations of sensory impairment with healthcare use and costs were estimated using the mixed-effects regression models. RESULTS: Of the 8982 respondents, 4346 (48.39%) were females and their mean (standard deviation) age at baseline was 57.03 (8.26) years. Individuals with hearing impairment (HI) only, visual impairment (VI) only, and dual sensory impairment (DSI) were all at significantly higher risks of healthcare use and catastrophic health expenditure than those without sensory impairment (all P < 0.05), except that VI only non-significantly prolonged inpatient days. Compared with no impairment, DSI was associated with increases in outpatient (ß = 50.67, 95% confidence interval [CI] = 17.47-83.86) and inpatient out-of-pocket costs (ß = 40.35, 95% CI = 5.94-74.76), while VI only or HI only did not show significant effects. Further stratification analyses indicated that the associations between sensory impairment and outpatient use were more pronounced among males than among females but that age group did not moderate the associations with any healthcare outcomes. CONCLUSIONS: HI and VI were independently and together associated with higher risks of healthcare use and catastrophic health expenditure. Dual sensory impairment was the only category consistently associated with increased outpatient and inpatient costs.

The coordinated development of manufacturing industry and logistics industry in the Yangtze River Economic Belt: Empirical study by stages based on Haken Model.

It has great significance for improving the logistics service ability of the Yangtze River economic belt, optimizing the industrial structure of manufacturing industry, and realizing the integrated development of the Yangtze River economic belt to explore the collaborative evolution of logistics industry and manufacturing industry in the Yangtze River economic belt, and identify the leading position of the collaborative development of the two industries, so as to. Based on the Haken Model, this paper summarizes the coevolution law of logistics industry and manufacturing industry in the Yangtze River economic belt through two-stage empirical analysis, and identifies the order parameters of the co-development of logistics industry and manufacturing industry. The results show that the overall degree of coordination between the logistics industry and the manufacturing industry in the Yangtze River economic belt is high. And the order parameter has been changed from manufacturing industry in 2003-2009 to logistics industry in 2010-2017. The gap between regions has been reduced, and the western region has the advantage of post development.

Catastrophic Health Expenditure Associated With Frailty in Community-Dwelling Chinese Older Adults: A Prospective Cohort Analysis.

Background: Catastrophic health expenditure (CHE) represents a key indicator for excessive financial burden due to out-of-pocket (OOP) healthcare costs, which could push the household into poverty and is highly pronounced in households with members at an advanced age. Previous studies have been devoted to understanding the determinants for CHE, yet little evidence exists on its association with frailty, an important geriatric syndrome attracting growing recognition. We thus aim to examine the relationship between frailty and CHE and to explore whether this effect is moderated by socioeconomic-related factors. Methods: A total of 3,277 older adults were drawn from two waves (2011 and 2013) of the China Health and Retirement Longitudinal Study (CHARLS). CHE was defined when OOP healthcare expenditure exceeded a specific proportion of the capacity of the household to pay. Frailty was measured following the Fried Phenotype (FP) scale. Mixed-effects logistic regression models were employed to assess the longitudinal relationship between frailty and CHE, and stratification analyses were conducted to explore the moderation effect. Results: The incidence of CHE among Chinese community-dwelling older adults was 21.76% in 2011 and increased to 26.46% in 2013. Compared with non-frail individuals, prefrail or frail adults were associated with higher odds for CHE after controlling for age, gender, residence, education, marriage, income, health insurance, smoking, drinking, and comorbidity (prefrail: odds ratio (OR) = 1.32, 95%CI = 1.14-1.52; frail: OR = 1.67, 95%CI = 1.13-2.47). Three frailty components including weakness, exhaustion, and shrinking contributed to a significantly increased likelihood of CHE (all p < 0.05), while the other two components including slowness and inactivity showed a non-significant effect (all p > 0.05). Similar effects from frailty on CHE were observed across socioeconomic-related subgroups differentiated by gender, residence, education, household income, and social health insurance. Conclusions: Frailty is a significant predictor for CHE in China. Developing and implementing cost-effective strategies for the prevention and management of frailty is imperative to protect households from financial catastrophe.

Economic Impact of Preoperative Meloxicam IV Administration in Total Knee Arthroplasty: A Randomized Trial Sub-Study.

We evaluated the economic impact associated with preoperative meloxicam IV 30 mg vs placebo administration among adult total knee arthroplasty (TKA) recipients enrolled in Phase IIIB NCT03434275 trial. Data on total hospital costs and length of stay (LOS) obtained from the trial were compared between meloxicam IV 30 mg and placebo groups. Patients in the meloxicam IV 30 mg vs placebo group (n = 93 vs 88) incurred an adjusted $2,266 (95% CI: -$1,035, $5,116; p = 0.1689) lower total hospital costs and an adjusted 8.6% (95% confidence interval [CI]: -2.0%, 18.1%; p = 0.1082) shorter LOS. While statistically non-significant, based on 95% CIs, the results from this sub-study may suggest a favorable impact associated with meloxicam IV 30 mg on hospital costs and LOS.

Assessment on chronic and transgenerational toxicity of methamphetamine to Caenorhabditis elegans and associated aquatic risk through toxicity indicator sensitivity distribution (TISD) analysis.

Evidence about the adverse effects of methamphetamine (METH) on invertebrates is scarce. Hence, C. elegans, a representative invertebrate model, was exposed to METH at environmental levels to estimate chronic and transgenerational toxicity. The results of chronic exposure were integrated into an underlying toxicity framework of METH in invertebrates (e.g., benthos) at environmentally relevant concentrations. The induction of cellular oxidative damage-induced apoptosis and fluctuation of ecologically important traits (i.e., feeding and locomotion) might be attributed by the activation of the longevity regulating pathway regulated by DAF-16/FOXO, and detoxification by CYP family enzymes. The adverse effects to the organism level included impaired viability and decreased fecundity. The results from transgenerational exposure elucidated the cumulative METH-induced damage in invertebrates. Finally, a new risk assessment method named toxicity indicator sensitivity distribution (TISD) analysis was proposed by combining multiple toxicity indicator test data (ECx) to derive the hazardous concentration for 10% indicators (C10) of one species. The risk quotient (RQ) values calculated by measured environmental concentrations and C10 in southern China, southeastern Australia, and the western US crossed the alarm line (RQ = 5), suggesting a need for long-term monitoring.

Fine Needle Biopsy Versus Core Needle Biopsy Combined With/Without Thyroglobulin or BRAF 600E Mutation Assessment for Detecting Cervical Nodal Metastasis of Papillary Thyroid Carcinoma.

Objectives: To analyze the diagnostic benefit of fine needle aspiration biopsy cytology (FNAB-C) and core needle biopsy tissue (CNB-T) with the addition of thyroglobulin (Tg) in the washout of the needle or BRAF V600E mutation assessment in assessing cervical lymph node metastasis (LNM) in papillary thyroid carcinoma. Materials and Methods: A total of 186 lymph nodes were punctured by fine or core needle. The diagnostic performance of FNAB-C and CNB-T with Tg in the washout or BRAF V600E mutation assessment was compared. Results: The optimal cutoff value of FNAB-Tg was 1.0 ng/ml, with an AUC of 0.976. The sensitivity and specificity of FNAB-C in predicting cervical LNM were 97.4% and 71.4%, respectively, and the addition of FNAB-Tg could contribute to a sensitivity of 100% and a specificity of 95%, but the introduction of BRAF V600E mutation assessment was associated with a decreased sensitivity of 96.3% and a decreased specificity of 50.0%. The FNAB-Tg level showed a comparable distribution in malignant lymph nodes with different TgAb statuses, serum TSH levels, and serum Tg levels. The sensitivity and specificity of CNB-T in predicting cervical LNM were 98.9% and 100%, respectively. The addition of CNB-Tg did not alter the diagnostic ability, but the introduction of BRAF V600E mutation assessment obtained the best performance, with a sensitivity of 100% and specificity of 100%. Conclusion: The sensitivity and specificity of FNAB-C could be increased if combined with FNAB-Tg. CNB-T alone could provide satisfactory diagnostic reliability.

Social Support and Mortality in Community-Dwelling Chinese Older Adults: The Mediating Role of Frailty.

PURPOSE: Population ageing is posing an unprecedented challenge globally, necessitating a better understanding of modifiable factors and underlying pathways that could contribute to health and longevity in older age. We thus aim to investigate how the modifiable social support (and its various sources) is related to mortality among older adults, as well as whether and to what extent geriatric frailty plays a role in mediating the relationship. METHODS: We included 11,934 community-dwelling adults (≥65) from four waves of the Chinese Longitudinal Healthy Longevity Survey (2008-2018). Frailty was constructed by 44 health deficits, following a validated frailty index scale. Social support was measured using a sum score of three dimensions (family support, social service and social security) with 22 items. The outcome was all-cause mortality. Multivariate logistic or linear regression models were employed when appropriate to assess the associations among social support, frailty and mortality. Mediation analysis was applied to examine the role of frailty underlying the pathway between social support and mortality risk. RESULTS: A higher sum score of social support at baseline reduced mortality risk during the 10-year follow-up period (AOR=0.947, 95% CI=0.917~0.977). Amongst three sources of social support, family support and social security availability showed significantly protective effect against mortality, while social service revealed only non-significant effect. A higher level in the overall social support (ß=-0.066, 95% CI=-0.113~-0.020) or family support (ß=-0.121, 95% CI=-0.202~-0.039) was also significantly associated with decreased frailty. Meanwhile, frailty partially mediated the relationship of mortality with the overall social support and family support, where the proportion of mediation equaled to 17.1% and 20.5%, respectively. CONCLUSION: Social support could be associated with reduced risks for frailty and mortality, and such protective influences are especially manifested in its family support component among Chinese older adults. Frailty functions as potential mediator underlying the association of mortality with social support and family support. Our findings indicate the importance of social support as an integral part of geriatric care and underline the potential benefits of frailty assessment and intervention.

Quantitative Assessment of Copper(II) in Wilson's Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering.

Cu2+ is closely related to the occurrence and development of Wilson's disease (WD), and quantitative detection of various copper indicators (especially liver Cu2 and urinary Cu2+) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu2+ detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in determining WD status in real-time. Herein, we rationally designed a type of Cu2+-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(N-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu2+ content and urinary Cu2+ in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), respectively. In the nanoprobe, one Raman molecule of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman molecule mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu2+ can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm-1 of MBN is amplified, while the SERS signal at 1378 cm-1 of NAT remains stable, generating a ratiometric SERS I2223/I1378 signal. Both NIR-II PA1250 nm and SERS I2223/I1378 signals of the nanoprobe show a linear relationship with the concentration of Cu2+. The nanoprobe was successfully applied for in vivo quantitative detection of liver Cu2+ of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu2+ of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.

A low-cost microfluidic platform coupled with light emitting diode for optogenetic analysis of neuronal response in C. elegans.

Optogenetic method is widely used for dissecting the neuronal function and connectivity in a specific neural circuit, which can help understanding how the animal process information and generate behavior. The nematode C. elegans has a simple but complete nervous system, making it an attractive model to study the dynamics signals of neural circuits. However, in vivo analysis on neural circuits usually rely on the complex and expensive optical equipment to allow optogenetic stimulating the neuron while recording its activities in such a freely moving animal. Hence, in this paper we reported a portable optofluidic platform that works based on optical fiber illumination and functional imaging for worm optogenetic manipulation. A light beam from LED laser pen crossing the 3D-printed optical fiber channel is used to activate the neurons specific-expressed with light sensitive proteins ChR-2. The imaging light path is perpendicular to the stimulation light, which allows activating neuron precisely and measuring cellular signals simultaneously. By using such an easy-to-assemble device, optical stimulation of the specific neurons and detection of dynamic calcium responses of other neurons could be proceeded simultaneously. Thus, the developed microfluidic platform puts forward a simple, rapid and low-cost strategy for further neural circuits studies.

Assessment of sugar and sugar accumulation-related gene expression profiles reveal new insight into the formation of low sugar accumulation trait in a sweet orange (Citrus sinensis) bud mutant.

The accumulation of soluble sugars in fleshy fruits largely determines their sweetness or taste. A spontaneous sweet orange mutant 'Hong Anliu' (HAL, Citrus sinensis) accumulates low soluble sugar content in fruit juice sacs than its wild type, 'Anliu' (AL) orange; however, the cause of reduced sugar content in 'HAL' fruit remains unclear. In this study, sugar content and expression profiles of genes involved in sugar metabolism and transport were compared between 'HAL' and 'AL' fruit juice sacs. In both cultivars, fructose and glucose displayed the increasing trends with significantly lower contents in 'HAL' than 'AL' after 160 DAF; moreover, sucrose had a declining trend in 'HAL' and increasing trend in 'AL' with fruit development. On the other hand, transcript levels of VINV, CWINV1, CWINV2, SUS4, SUS5, SPS1, SPS2, VPP-1, VPP-2, and some sugar transporter genes were significantly decreased in 'HAL' compared with 'AL' after 100 DAF or 160 DAF. Interestingly, the transcript levels of SPS2 and SUT2 exhibited a similar trend as it was found for sucrose content in both cultivars. These results suggested that the low sugar accumulation in 'HAL' fruit JS is accompanied by the reduced sink strength, sucrose-synthesis ability, and vacuolar storage ability compared with 'AL'; reduction of CWINVs, VINV, SPS2, SUT2, VPP-1, and VPP-2 transcript levels possibly plays a key role in the low storage of soluble sugars in the vacuoles of mutant juice sacs.

Maternal ambient air pollution exposure with spatial-temporal variations and preterm birth risk assessment during 2013-2017 in Zhejiang Province, China.

Preterm birth (PTB) can give rise to significant neonatal morbidity and mortality, as well as children's long-term health defects. Many studies have illustrated the associations between ambient air pollution exposure during gestational periods and PTB risks, but most of them only focused on one single air pollutant, such as PM2.5. In this population-based environmental-epidemiology study, we recruited 6275 pregnant mothers in Zhejiang Province, China, and evaluated their gestational exposures to various air pollutants during 2013-2017. Time-to-event logistic regressions were performed to estimate risk associations after adjusting all confounders, and Quasi-AQI model and PCA-GLM analysis were applied to resolve the collinearity issues in multi-pollutant regression models. It was found that gestational exposure to ambient air pollutants was significantly associated with the occurrence of PTB, and SO2 was the largest contributor with a proportion of 29.4%. Three new variables, prime factor (a combination of PM2.5, PM10, SO2, and NO2), carbon factor (CO), and ozone factor (O3), were generated by PCA integration, contributing 63.4%, 17.1%, and 19.5% to PTB risks, respectively. The first and third trimester was the most crucial exposure window, suggesting the pregnant mothers better to avoid severe air pollution exposures during these sensitive periods.