Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents.

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Intraplate thrust orogeny of the Altai Mountains revealed by deep seismic reflection.

The Altai orogen is a typical intracontinental orogen in Central Asia that experienced far-field deformation associated with Indian-Eurasian plate convergence. This region is characterized by uplift comparable to that of the Tianshan Mountains but has a distinct strain rate. Half of the Indo-Asia strain is accommodated by the Tianshan Mountains, whereas the Altai Mountains accommodates only 10%. To elucidate how the Altai Mountains produced such a large amount of uplift with only one-fifth of the strain rate of the Tianshan Mountains, we constructed a detailed crustal image of the Altai Mountains based on a new 166.8-km deep seismic reflection profile. The prestack migration images reveal an antiform within the Erqis crust, an âˆ¼10 km Moho offset between the Altai arc and the East Junggar area, and a major south-dipping (30° dip) thrust in the lower crust beneath the Altai Mountains, which is connected to the Moho offset. The south-dipping thrust not only records the southward subduction of the Ob-Zaisan Ocean in the Paleozoic but also controlled the Altai deformation pattern in the Cenozoic with the Erqis antiform. The Erqis antiform prevented the extension of deformation to the Junggar crust. The south-dipping thrust in the lower crust of the Altai area caused extrusion of the lower crust, generating uplift at the surface, thickening of the crust, and steep (∼10 km) Moho deepening in the Altai Mountains. This process significantly widened the deformation zone of the Altai Mountains. These findings provide a new geodynamic model for describing how inherited crustal structure controls intraplate deformation without strong horizontal stress.

Microbiological isolates and associated complications of dacryocystitis and canaliculitis in a prominent tertiary ophthalmic teaching hospital in northern China.

BACKGROUND: To report the microbiological isolates, aetiology, complications, antibiotic susceptibilities, and clinical remission of dacryocystitis and canaliculitis in a prominent tertiary ophthalmic teaching and referral hospital located in northern China and to offer appropriate recommendations for preventing and formulating drug treatment strategies. METHODS: This prospective study recruited a total of 477 participants who had been diagnosed with either dacryocystitis or canaliculitis. The cohort comprised 307 patients with chronic dacryocystitis, 111 patients with acute dacryocystitis, and 59 patients with canaliculitis. Purulent discharge from the lacrimal duct was collected using a sterile swab and immediately subjected to microbial culture. Antimicrobial susceptibility testing was conducted following established protocols. All participants were scheduled for follow-up visits within 14 days after receiving antibiotic therapy. RESULTS: The present findings indicated that women exhibited a higher susceptibility to the condition, as evidenced by the occurrence of 367 cases in comparison to 110 cases among men. Among the 477 patients, definitive causes were established in 59 individuals, accounting for 12.4% of the patients. Additionally, ocular complications were reported by 132 patients, representing 27.7% of the total. Monocular involvement was observed in the majority of cases, with 402 out of 477 patients (84.3%) affected, while binocular involvement was present in 75 patients (15.7%). In total, 506 microbiological strains were recovered from 552 eyes, with Staphylococcus epidermidis (16.4%) being the most prevalent microorganism. Other predominant isolates included Corynebacterium macginleyi (9.1%), Staphylococcus aureus (5.1%), Streptococcus pneumoniae (4.9%), Haemophilus (4.4%), Propionibacterium acnes (3.5%), and Eikenella corrodens (3.1%). Among the 12 isolated fungi, Candida parapsilosis accounted for 66.7%. The susceptibility to antimicrobial agents tested in gram-negative bacilli (79.5%) was observed to be higher than that of anaerobic bacteria (76.7%) and gram-positive cocci (55.4%). With pharmacological therapy, the remission rate of acute dacryocystitis (72.7%) was found to be higher than that of canaliculitis (53.3%) and chronic dacryocystitis (42.3%). CONCLUSIONS: This study highlights the microbial spectrum of dacryocystitis and canaliculitis, particularly C.macginleyi, E.corrodens and C.parapsilosis, which are also more frequently isolated. Vancomycin and imipenem may be more effective treatment options. Most cases have an unknown aetiology, and essential preventive measures involve postoperative cleansing of the lacrimal passage following eye and nasal surgeries, as well as the proactive management of rhinitis.

Improved quantification of carbonyl sub-metabolome by liquid chromatography mass spectrometry using a fragment controlled multiplexed isotopic tag.

BACKGROUND: Carbonyl-containing metabolites are a class of key intermediate in metabolism, which has potentials to be biomarkers. Since their poor ionization, derivatization reagents, such as dansylhydrazine, are usually used to improve the sensitivity and/or to facilitate quantification. However, most current carbonyl derivatization reagents only have two channels, one is isotopically labeled and the other one is non-labeled. To quantify more samples in a run and using data-independent acquisition (DIA) mode to get comprehensive and unbiased mass fragmentation, we proposed a fragment-controlled isotopic tag, called DiMe-FP-NHNH2 (FP) which has five channels: Δ0, Δ3, Δ6, Δ9, and Δ12, thus up to 5 samples can be analyzed in a run. RESULTS: The most important improvement is that the FP tag can produce multiple characteristic signals in tandem mass, diagnostic ions and neutral losses, which helps to selectively detect aldehydes/ketones for targeted and untargeted analysis. To exhibit all capabilities of the FP tag, we mimicked an untargeted metabolomics experiment, which comprises two steps. First, discovery step, using Data-Independent Analysis (SWATH-MS) and the labeling of two channels (Δ0 and Δ3), we picked out aldehyde/ketone from the pooled urine samples based on three characteristic signals, including isotope patterns, diagnostic ions, and neutral losses. Second, five-plex quantification, relative and absolute quantification were achieved in a single LC-MS analysis. Notably, because of different nominal masses, the FP tag can be used on any low or high resolution mass spectrometers. SIGNIFICANCE: The benefits and performance of the FP tag are demonstrated by the analysis of urine samples collected from patients from a prostate cancer study, in which more than a thousand features were found based on MS1 fingerprint, but only around 120 aldehyde/ketone candidates were confirmed with characteristic signals and nine of which were quantified showing significant differences from healthy and reference urine samples.

Quality of childcare and delayed child development in left-behind children in China.

BACKGROUND: Inequalities in job opportunities and income prompts many Chinese parents to leave rural regions to work in urban regions. Their children are left behind in rural regions, subjected to worse quality of childcare that jeopardizes their development. This study aimed to examine the association between quality of childcare and delayed child development in under-three years children left behind in China. METHODS: Cross-sectional national survey was conducted in children left behind in rural China in 2017. Exploratory and confirmatory factor analysis was used to develop a quality of childcare index. Mutlilevel analyses determined factors associated with quality of childcare and child development on a province and individual level. RESULT: The largest population of at-risk children left behind were found in higher-GDP provinces. Children left behind had the lowest mean quality of childcare score. Multilevel analysis found that province level accounted for a great proportion of variance observed. CONCLUSIONS: While migration to urban regions for work may improve household income, a trade-off in worse quality of childcare and developmental delays exists. With improving household income often being the greatest contributing factor for parental migration, policies to reduce inequalities in job opportunities and wealth between rural and urban regions are required. IMPACT: Previous studies identified higher prevalence of developmental delays in children left behind in China. However, quality of childcare has not been examined. Based on WHO's Nurturing Care Framework, we developed a quality of childcare index to assess its association with child development in children left behind. Greatest proportion of children left behind at-risk of developmental delays resided in higher-GDP states, indicating a trade-off in worse quality of childcare and developmental delays. Since improving household income is the main factor for parental migration, policies to close inequalities in job opportunities and wealth between rural and urban regions are required.

Recent Progress in Two-Dimensional Material Exfoliation Technology and Enlightenment for Geological Sciences.

Mechanical exfoliation technology is vital for the development of two-dimensional (2D) materials. This technology has also facilitated the verification of the performance of electronic and optical devices made from 2D materials. In this Perspective, we provide an overview of exfoliation techniques and highlight key physical properties. Additionally, we explored the chemical instability of certain 2D materials and proposed practical solutions to enhance their stability. Furthermore, we discuss the advantages of suspended 2D materials, which demonstrate improved compatibility and properties compared to nonsuspended materials. A particularly intriguing aspect of this Perspective is the exploration of the similarities between the Earth's crust and 2D materials, offering insights into the formation mechanisms of geological phenomena. In this context, 2D materials may serve as simulators for studying geological processes. We hope that this Perspective stimulates further research into exfoliation technology and the physical/chemical properties of 2D materials while providing new inspiration for earth science investigations.

Fragmentation of continental subduction is ending the Himalayan orogeny.

After two continents collide, plate convergence and orogenesis are sustained because subducted continental lithosphere continues pulling the surface plate. It remains controversial how, why, and when continental plate convergence and collision slow down and eventually cease. We use an unprecedented data coverage and present a regional-scale seismic tomographic image of the mantle structure beneath the Tibetan Plateau. In the mantle transition zone, we identify multiple high-velocity anomalies and interpret them as detached pieces of the Indian continental slab. Facilitated by internal heterogeneity of the continental lithosphere, piecewise slab detachments could reduce the slab pull force, resulting in the Miocene slowdown of the India-Eurasia convergence and coeval diachronous potassic volcanism in southern Tibet. We propose that slab detachment is a mechanism that eventually will lead to the end of the Indo-Eurasian continental collision and the Himalayan orogeny.

A pilot study of Kangaroo mother care in early essential newborn care in resource-limited areas of China: the facilitators and barriers to implementation.

BACKGROUND: Implementation of Kangaroo Mother Care (KMC) in resource-limited areas of China may face unique barriers, such as a lack of resources, geographic location and more traditional culture among others. This qualitative study analyses the facilitators and barriers to implementing KMC in county-level health facilities in resource-limited areas of China for the promotion of KMC on a larger scale. METHODS: Participants from 4 of the 18 pilot counties where early essential newborn care was implemented through the Safe Neonatal Project and 4 control counties not enrolled in Safe Neonatal Project were selected using purposive sampling. A total of 155 participants were interviewed, including stakeholders of the Safe Neonatal Project such as national maternal health experts, relevant government officials and medical staff. Thematic analysis was used to process and analyse the interview content in order to summarise the facilitators and barriers to implementing KMC. RESULTS: KMC was accepted in the pilot areas but still faced certain challenges due to institutional regulation, resource provision and the perceptions of health staff, postpartum mothers and their families as well as COVID-19 prevention and control regulations. The facilitators identified were government officials and medical staff acceptance and the incorporation of KMC into routine clinical care. The barriers identified were a lack of dedicated funding and other resources, the present scope of health insurance and KMC cost-sharing mechanism, providers' knowledge and practical abilities, parental awareness, postpartum discomfort, fathers' inadequate involvement, and the impact from COVID-19. CONCLUSION: The Safe Neonatal Project pilot experience indicated the feasibility of implementing KMC in more areas of China. Optimising institutional regulations, providing necessary supporting resources and enhancing education and training may help to refine the implementation and scale-up of KMC practice in China.

Association of duration of skin-to-skin contact after cesarean delivery in China: a superiority, multicentric randomized controlled trial.

BACKGROUND: In China, the rates of early initiation and exclusive breastfeeding are low. The high cesarean delivery rates further contribute to low breastfeeding outcomes. Skin-to-skin contact, a key component of early essential newborn care, is known to be associated with improved breastfeeding initiation and exclusivity; however, the necessary duration has not been subjected to a randomized control trial. OBJECTIVE: This study aimed to determine the association of the duration of skin-to-skin contact after cesarean delivery with breastfeeding outcomes and maternal and neonatal health outcomes in China. STUDY DESIGN: This was a multicentric randomized controlled trial that was conducted at 4 hospitals in China. A total of 720 participants at ≥37 gestational weeks with a singleton pregnancy and who received an elective cesarean delivery with epidural anesthesia or spinal anesthesia or combined spinal-epidural anesthesia were randomly divided into 4 groups at a ratio of 1:1:1:1. The control group received routine care. Intervention group 1 (G1), 2 (G2), and 3 (G3) received 30, 60, and 90 minutes of skin-to-skin contact immediately after the cesarean delivery, respectively. RESULTS: Between January 3 and October 14, 2021, 659 participants were recruited, including 173 in the control group, 176 in G1, 146 in G2, and 164 in G3. Among G1, G2, and G3, the rate of early initiation of breastfeeding within 60 minutes of birth was 56%, 71%, and 72%, respectively, compared with 22% in the control group (P<.001). The exclusive breastfeeding rate at discharge was 69%, 62%, and 71%, respectively, compared with 57% in the control group (P=.003). Early essential newborn care practices were associated with a reduction in postpartum blood loss and neonatal intensive care unit or neonatal ward admission (P<.001; P=.022) . CONCLUSION: Our findings highlight that prolonged skin-to-skin contact after a cesarean delivery was associated with higher initiation and exclusive breastfeeding at discharge rates. It also found associations with reduced postpartum blood loss and neonatal intensive care unit or neonatal ward admission.

Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury.

Astrocytes and microglia play an orchestrated role following spinal cord injury; however, the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood. Herein, microglia were pharmacologically depleted and the effects on the astrocytic response were examined. We further explored the potential mechanisms involving the signal transducers and activators of transcription 3 (STAT3) pathway. For in vivo experiments, we constructed a contusion spinal cord injury model in C57BL/6 mice. To deplete microglia, all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397, starting 2 weeks prior to surgery until they were sacrificed. Cell proliferation was examined by 5-ethynyl-2-deoxyuridine (EdU) and three pivotal inflammatory cytokines were detected by a specific Bio-Plex ProTM Reagent Kit. Locomotor function, neuroinflammation, astrocyte activation and phosphorylated STAT3 (pSTAT3, a maker of activation of STAT3 signaling) levels were determined. For in vitro experiments, a microglia and astrocyte coculture system was established, and the small molecule STA21, which blocks STAT3 activation, was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia. PLX3397 administration disrupted glial scar formation, increased inflammatory spillover, induced diffuse tissue damage and impaired functional recovery after spinal cord injury. Microglial depletion markedly reduced EdU+ proliferating cells, especially proliferating astrocytes at 7 days after spinal cord injury. RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397. Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes. Importantly, in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration. These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation, and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.

Chemical isotope labeling for quantitative proteomics.

Advancements in liquid chromatography and mass spectrometry over the last decades have led to a significant development in mass spectrometry-based proteome quantification approaches. An increasingly attractive strategy is multiplex isotope labeling, which significantly improves the accuracy, precision and throughput of quantitative proteomics in the data-dependent acquisition mode. Isotope labeling-based approaches can be classified into MS1-based and MS2-based quantification. In this review, we give an overview of approaches based on chemical isotope labeling and discuss their principles, benefits, and limitations with the goal to give insights into fundamental questions and provide a useful reference for choosing a method for quantitative proteomics. As a perspective, we discuss the current possibilities and limitations of multiplex, isotope labeling approaches for the data-independent acquisition mode, which is increasing in popularity.

Effectiveness of early essential newborn care implementation in four counties of western China.

BACKGROUND: Neonatal survival is a public health concern globally. However, the regional disparity in neonatal mortality between rural counties of western China and urban areas of eastern provinces remains high. Early essential newborn care (EENC), recommended by World Health Organization, refers to a set of cost-effective interventions to improve neonatal health and development outcomes. In this study, we aimed to explore the effectiveness of EENC implementation in four counties of western China. METHODS: Pre- and post-intervention investigations were conducted in four selected EENC intervention counties and four control counties of four western provinces of China, from June to August 2017 and from December 2020 to April 2021 respectively. A mixed quantitative and qualitative approach was used for data collection and analysis. Data on the coverage of EENC practices were collected via a post-intervention face-to-face questionnaire survey with postpartum mothers before hospital discharge. Hospital-reported data on neonatal health indicators were obtained through mail surveys in both investigations. We also performed semi-structured interviews with policymakers, health staff and postpartum mothers to understand their perceptions about the usefulness of EENC implementation. RESULTS: Overall, 599 mother-newborn pairs in the intervention group and 699 pairs in the control group participated in the post-intervention survey. Controlling for the confounding factor of province, the proportion of newborns receiving EENC interventions was higher in the intervention group than in the control group (P < 0.05). Intervention groups in four provinces had higher coverage of: any skin-to-skin contact (99.50% vs. 49.07%); early breastfeeding initiation (within 60 min of birth) (90.84% vs. 80.35%); no medicine applied to the umbilical cord (98.50% vs. 9.73%); routine eye care (93.16% vs. 8.73%); and vitamin K1 administration (98.33% vs. 88.98%). EENC implementation was associated with decreased risk of neonatal diarrhea (OR: 0.326, 95% CI: 0.123, 0.865) and eye infection (OR: 0.147, 95% CI: 0.045, 0.483). Policymakers, health staff and postpartum mothers expressed satisfaction with the EENC interventions, noting a willingness among staff and policymakers to implement and sustain these interventions; the promotion of these interventions within hospital policy; the positive emotions experienced by postpartum mothers; perceived improvements in health; and improvements in support for health workers. CONCLUSION: EENC-recommended core practices (except kangaroo mother care) have been successfully introduced in pilot hospitals. The efficacy of EENC implementation should be highly recognized to accelerate the progress towards its national roll out.

Analysis of illicit pills and drugs of abuse in urine samples using a 3D-printed open port probe hyphenated with differential mobility spectrometry-mass spectrometry.

The present work describes the application of an in-house developed 3D-printed open port probe (3DP-OPP) with differential ion mobility spectrometry (DMS) mass spectrometry. Targeted quantitative analysis in urine was performed with a triple quadrupole mass spectrometer in the selected reaction monitoring mode (OPP-DMS-SRM/MS) and illicit pill screening using data independent acquisition (OPP-DMS-SWATH/MS). The combination of compensation voltage (CoV) scanning in DMS using modifiers with SWATH/MS acquisition for MS/MS spectrum generation enabled the differentiation of isobaric signals with a large dynamic range and enhance the information contained in the screening of illicit ecstasy pills. As for any direct MS introduction technique where no chromatographic separation is applied DMS with acetonitrile as a modifier allows the separation of cocaine and tramadol, and their isomeric metabolites in urine samples. Quantitative application using OPP-DMS-SRM/MS is presented without the need for sample preparation with a lower limit of quantification at 10-25 ng mL-1 for the analytes and less than 40 seconds for sample to sample analysis.

Functionalized Fluorescent Nanodiamonds for Simultaneous Drug Delivery and Quantum Sensing in HeLa Cells.

Here, we present multifunctional fluorescent nanodiamonds (FNDs) for simultaneous drug delivery and free radical detection. For this purpose, we modified FNDs containing nitrogen vacancy (NV) centers with a diazoxide derivative. We found that our particles enter cells more easily and are able to deliver this cancer drug into HeLa cells. The particles were characterized by infrared spectroscopy, dynamic light scattering, and secondary electron microscopy. Compared to the free drug, we observe a sustained release over 72 h rather than 12 h for the free drug. Apart from releasing the drug, with these particles, we can measure the drug's effect on free radical generation directly. This has the advantage that the response is measured locally, where the drug is released. These FNDs change their optical properties based on their magnetic surrounding. More specifically, we make use of a technique called relaxometry to detect spin noise from the free radical at the nanoscale with subcellular resolution. We further compared the results from our new technique with a conventional fluorescence assay for the detection of reactive oxygen species. This provides a new method to investigate the relationship between drug release and the response by the cell via radical formation or inhibition.

Correlates of suicidal ideation in rural Chinese junior high school left-behind children: A socioecological resilience framework.

Introduction: Suicide is one of the top five causes of adolescent mortality around the world. The socioecological resilience framework in explaining the risk factors and protective factors for suicidal ideation in left-behind children (LBC) has not been well explored. The current study aims to compare the prevalence of suicidal ideation in LBC and non-LBC, and explore its correlations with resilience factors among LBC. Methodology: This study was part of an epidemiological survey conducted by UNICEF exploring mental health outcomes in left-behind children. We implemented a cross-sectional study collecting data from 11 provinces and 1 municipal, with 5,026 participants (3,359 LBC, 1,667 controls) in year one junior high school living in impoverished areas of rural China. Data on suicidal ideation, self-harm, resilience factors including health-risk behaviors, psychological wellbeing as it was measured by the Strengths and Difficulties Questionnaire, peer relationship within the school environment, and family support were collected. Results: Overall prevalence of suicidal ideation among LBC was 7.2% which is significantly different from 5.5% reported by NLBC (χ2 = 4.854, p = 0.028). LBC reported a higher prevalence of self-harm (16.4%) than NLBC (13.0%; χ2 = 10.232, p = 0.001), but there was no difference in the prevalence of suicide plan, suicide attempt or help-seeking. LBC had significantly poorer psychological feeling, and greater emotional and behavioral difficulties peer relationship in the school environment than controls. In the multiple logistic regression, history of self-harm was the greatest predictor for suicidal ideation among LBC (OR = 2.078, 95% CI: 1.394-3.100, p < 0.001). Health risk behavior including previous smoking attempt, poor psychological feeling, and emotional and behavior difficulties, and poor peer relationship within school environment, were also significant risk factors for suicidal ideation among LBC. Conclusion: The prevalence of suicidal ideation and self-harm was greater among left-behind than non-left-behind children. Our results show resilience factors including previous self-harm, emotional and behavioral problems, smoking, and poor peer relationship are significantly associated with suicidal ideation in left-behind adolescents.

Research on the Matching Relationship between the Supply of Urban Ecological Recreational Space and the Demand of Residents-A Case Study of an Urban Development Area in Wuhan.

An urban ecological recreational space (UERS), which connects the natural environment with urban residents, is an important guarantee for developing a livable city and improving the well-being of residents. However, there is a serious imbalance between the supply of UERSs and the demand of residents in many big, rapidly developing cities. Previous studies usually used indicators such as scale or quantity to measure the supply level of UERS enjoyed by residents, ignoring its own quality differences. Therefore, taking the urban development area of Wuhan as the research object, we measured the quality of UERS from four dimensions using the entropy method and designed a method to measure the supply service level under the hierarchical travel threshold to analyze the supply level of UERSs based on a community unit. Finally, combined with the demand characteristics of different groups, the matching relationship between supply and demand of UERSs in each community is quantitatively analyzed. The results show the following: (1) The quality of UERS in urban development area of Wuhan varies greatly and its distribution is extremely uneven. (2) The level of supply services and the demand level vary greatly, and the overall performance has a trend of decreasing from the city center to the periphery. (3) The overall matching relationship between supply and demand of UERS is not ideal, and more than half of the communities are in supply deficit or without services. Our study provides a novel perspective on quantifying the supply-demand relationship of UERS. It can more accurately guide decision-makers and planners in determining areas with mismatches between the supply and demand of UERSs and in making targeted layouts of UERSs and relevant policies.

The Isotopic Ac-IP Tag Enables Multiplexed Proteome Quantification in Data-Independent Acquisition Mode.

Data-independent acquisition (DIA) is an increasingly used approach for quantitative proteomics. However, most current isotope labeling strategies are not suitable for DIA as they lead to more complex MS2 spectra or severe ratio distortion. As a result, DIA suffers from a lower throughput than data-dependent acquisition (DDA) due to a lower level of multiplexing. Herein, we synthesized an isotopically labeled acetyl-isoleucine-proline (Ac-IP) tag for multiplexed quantification in DIA. Differentially labeled peptides have distinct precursor ions carrying the quantitative information but identical MS2 spectra since the isotopically labeled Ac-Ile part leaves as a neutral loss upon collision-induced dissociation, while fragmentation of the peptide backbone generates regular fragment ions for identification. The Ac-IP-labeled samples can be analyzed using general DIA liquid chromatography-mass spectrometry settings, and the data obtained can be processed with established approaches. Relative quantification requires deconvolution of the isotope envelope of the respective precursor ions. Suitability of the Ac-IP tag is demonstrated with a triplex-labeled yeast proteome spiked with bovine serum albumin that was mixed at 10:5:1 ratios, resulting in measured ratios of 9.7:5.3:1.1.

The polymorphisms of FGFR2 and MGAT5 affect the susceptibility to COPD in the Chinese people.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by incomplete reversible airflow limitation and chronic inflammatory response lesions. This study mainly explored whether FGFR2 and MGAT5 polymorphisms affected the risk of COPD in the Chinese people. METHODS: Five variants in FGFR2 and MGAT5 were chosen and genotyped using Agena MassARRAY platform from 315 COPD patients and 314 healthy controls. The correlation of FGFR2 and MGAT5 with COPD susceptibility was evaluated with odds ratio (OR) and 95% confidence interval (CI) via logistic regression. RESULTS: We found rs2420915 enhanced the risk of COPD, while rs6430491, rs2593704 reduced the susceptibility of COPD (p < 0.05). Rs2420915 could promote the incidence of COPD in the elderly and nonsmokers. Rs1907240 and rs2257129 also increased the susceptibility to COPD in nonsmokers (p < 0.05). MGAT5-rs2593704 played a protective role in COPD development in different subgroups (age ≤ 70, male, smokers, and individuals with BMI ≤ 24 kg/m2). Meanwhile, rs6430491 was linked with a lower risk of COPD in nonsmoking and BMI ≤ 24 kg/m2 subgroups. CONCLUSIONS: We concluded that FGFR2 and MGAT5 genetic polymorphisms are correlated with the risk of COPD in the Chinese people. These data underscored the important role of FGFR2 and MGAT5 gene in the occurrence of COPD and provided new biomarkers for COPD treatment. TRIAL REGISTRATION: NA.

Development of curcumin-loaded zein nanoparticles for transport across the blood-brain barrier and inhibition of glioblastoma cell growth.

Glioblastoma (GBM) is a devastating primary brain tumor resistant to conventional therapies. A major obstacle to GBM treatment is the blood-brain barrier (BBB), or blood-glioma barrier, which prevents the transport of systemically administered (chemotherapeutic) drugs into the tumor. This study reports the design of dodecamer peptide (G23)-functionalized polydopamine (pD)-coated curcumin-loaded zein nanoparticles (CUR-ZpD-G23 NPs) that efficiently traversed the BBB, and delivered curcumin to glioblastoma cells. The NPs enhanced the cellular uptake of curcumin by C6 glioma cells compared to free curcumin, and showed high penetration into 3D tumor spheroids. Functionalization of the NPs with G23 stimulated BBB crossing and tumor spheroid penetration. Moreover, the NPs markedly inhibited proliferation and migration and induced cell death in liquid and soft agar models of C6 glioma cell growth. Fluorescence microscopy and flow cytometry studies showed that the CUR-ZpD-G23 NPs increased cellular ROS production and induced apoptosis of C6 glioma cells. Following in vivo intravenous injection in zebrafish, ZpD-G23 NPs demonstrated the ability to circulate, which is a first prerequisite for their use in targeted drug delivery. In conclusion, zein-polydopamine-G23 NPs show potential as a drug delivery platform for therapy of GBM, which requires further validation in in vivo glioblastoma models.