A cofunctional grouping-based approach for non-redundant feature gene selection in unannotated single-cell RNA-seq analysis.

Feature gene selection has significant impact on the performance of cell clustering in single-cell RNA sequencing (scRNA-seq) analysis. A well-rounded feature selection (FS) method should consider relevance, redundancy and complementarity of the features. Yet most existing FS methods focus on gene relevance to the cell types but neglect redundancy and complementarity, which undermines the cell clustering performance. We develop a novel computational method GeneClust to select feature genes for scRNA-seq cell clustering. GeneClust groups genes based on their expression profiles, then selects genes with the aim of maximizing relevance, minimizing redundancy and preserving complementarity. It can work as a plug-in tool for FS with any existing cell clustering method. Extensive benchmark results demonstrate that GeneClust significantly improve the clustering performance. Moreover, GeneClust can group cofunctional genes in biological process and pathway into clusters, thus providing a means of investigating gene interactions and identifying potential genes relevant to biological characteristics of the dataset. GeneClust is freely available at https://github.com/ToryDeng/scGeneClust.

Factors affecting delays in seeking treatment among malaria patients during the pre-certification phase in China.

BACKGROUND: Delays in malaria treatment can not only lead to severe and even life-threatening complications, but also foster transmission, putting more people at risk of infection. This study aimed to investigate the factors influencing treatment delays among malaria patients and their health-seeking behaviour. METHODS: The medical records of 494 patients diagnosed with malaria from 6 different malaria-endemic provinces in China were analysed. A bivariate and multivariable regression model was used to investigate the association between delays in seeking treatment and various factors. A Sankey diagram was used to visualize the trajectories of malaria patients seeking medical care. Total treatment delays were categorized as patient delays and doctor delays. RESULTS: The incidence of total delays in seeking malaria treatment was 81.6%, of which 28.4% were delayed by patients alone and 34.8% by doctors alone. The median time from the onset of symptoms to the initial healthcare consultation was 1 day. The median time from the initial healthcare consultation to the conclusive diagnosis was 2 day. After being subjected to multiple logistic regression analysis, living in central China was less likely to experience patient delays (OR = 0.43, 95% CI 0.24-0.78). The factors significantly associated with the lower likelihood of doctor delays included: age between 30 to 49 (OR = 0.43, 95% CI 0.23-0.81), being single/divorce/separated (OR = 0.48, 95% CI 0.24-0.95), first visiting a county-level health institution (OR = 0.25, 95% CI 0.14-0.45), first visiting a prefectural health institution (OR = 0.06, 95% CI 0.03-0.12) and first visiting a provincial health institution (OR = 0.05, 95%CI 0.02-0.12). Conversely, individuals with mixed infections (OR = 2.04, 95% CI 1.02-4.08) and those experiencing periodic symptoms (OR = 1.71, 95% CI 1.00-2.92) might face increased doctor delays. Furthermore, higher financial burden and complications were found to be associated with patient delays. Doctor delays, in addition to incurring these two consequences, were associated with longer hospital stays. CONCLUSION: There was a substantial delay in access to health care for malaria patients before China was certified malaria free. Region, marital status, periodic symptoms and the level of health institutions were factors contributing to delays in treatment-seeking among malaria patients.

Clinical features and treatment of apoplectic intratumoral hemorrhage of glioma.

OBJECTIVE: The primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease. METHODS: We analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection. RESULTS: We performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively. CONCLUSIONS: Patients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.

A New Design for Forearm Skin Flaps for Areas that Do not Require Additional Grafting.

Forearm skin flaps are widely used to reconstruct oral cancer due to their advantages, such as vascular stability, simple preparation, and a high success rate. However, traditional forearm skin flaps have shortcomings: the donor site requires grafting, which increases surgical trauma by creating a second surgical area, and the scarring at the donor site significantly affects the esthetics of the forearm. Therefore, we have designed a new ^-shaped radial forearm skin flap, in which the flap is designed as 2 semi-elliptical subunits. After the flap is harvested, these 2 subunits are joined, and the reserved skin at the donor site is directly sutured to the outer part of the donor site. The area of the ^-shaped radial forearm skin flap can be as large as that prepared with traditional forearm skin flaps, and there is no need for grafting at the donor site. This avoids additional trauma to the donor site after surgery, significantly reduces related complications, and enhances the esthetic outcome. This paper reports a case of a cheek cancer (carcinoma of the buccal mucosa) patient (T3N0M0), where the flap survived postoperatively, and both the surgical site and donor site healed in the first phase. The patient has no sensory or functional impairments; swallowing and speech functions are satisfactory.

LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway.

BACKGROUND: Increasing evidence highlights the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of renal cell carcinoma (RCC). Here, we explored the mechanism of AGAP2-AS1 in the occurrence and development of clear cell RCC (ccRCC) involving IGF2BP3/miR-9-5p/THBS2. METHODS: The expressions of AGAP2-AS1, IGF2BP3, miR-9-5p, and THBS2 and their relationship were analyzed by bioinformatics. The targeting relationship between AGAP2-AS1 and miR-9-5p and between miR-9-5p and THBS2 was evaluated with their effect on cell biological behaviors and macrophage polarization assayed. Finally, we tested the effect of AGAP2-AS1 on ccRCC tumor formation in xenograft tumors. RESULTS: IGF2BP3 could stabilize AGAP2-AS1 through m6A modification. AGAP2-AS1 was highly expressed in ccRCC tissues and cells. The lentivirus-mediated intervention of AGAP2-AS1 induced malignant behaviors of ccRCC cells and led to M2 polarization of macrophages. In addition, THBS2 promoted M2 polarization of macrophages by activating the PI3K/AKT signaling pathway. AGAP2-AS1 could directly bind with miR-9-5p and promote the expression of THBS2 downstream of miR-9-5p. These results were further verified by in vivo experiments. CONCLUSION: AGAP2-AS1 stabilized by IGF2BP3 competitively binds to miR-9-5p to up-regulate THBS2, activating the PI3K/AKT signaling pathway and inducing macrophage M2 polarization, thus facilitating the development of RCC.

Using Time Trade-Off Values to Estimate EQ-5D-Y Value Sets: An Exploratory Study.

OBJECTIVES: The published international EQ-5D-Y-3L valuation protocol does not recommend the composite time trade-off (cTTO) method as the primary valuation method because of 2 major concerns. First, the cTTO method was shown to generate high values. Second, the cTTO method is not as feasible for valuing children's health as other established methods. This study aimed to explore the feasibility of using cTTO values alone to estimate EQ-5D-Y-3L value sets. METHODS: We analyzed the cTTO data derived from the recently completed Chinese EQ-5D-Y-3L valuation study in which a total of 28 health states were valued. We assessed the feasibility of the cTTO tasks in terms of survey completion time and participant-reported difficulty of understanding the task, differentiating the health states, and deciding the answer. We also examined the data distribution characteristics and modeled the data using different models. RESULTS: In total, 418 participants completed the cTTO interview. On average, participants took approximately 35.70 minutes (SD 12.42) to complete the interview and made 13.21 moves (SD 9.00) in the cTTO tasks. There were 74.16%, 59.33%, and 11.48% of participants indicated that it was easy to understand the cTTO tasks, easy to differentiate between the health states, and difficult to decide on an indifference point, respectively. The data distribution was smooth, and a random-effects model performed the best in terms of coefficient significance, monotonicity, and predictive accuracy. CONCLUSION: Our finding suggests that estimating EQ-5D-Y-3L value sets using cTTO data alone is feasible and therefore could be considered as an option in future valuation studies for EQ-5D-Y-3L.

In situ click chemistry-based discovery of 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs by exploiting the tolerant region I in binding pocket.

HIV-1 reverse transcriptase (RT) is considered as one of the most significant targets for the anti-HIV-1 drug design due to their determined mechanism and well-decoded crystal structure. As a part of our continuous efforts towards the development of potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) by exploiting the tolerant region I of NNRTIs binding pocket (NNIBP), the miniaturized parallel synthesis via CuAAC click chemistry reaction followed by in situ biological screening have been performed in this work. The in situ enzyme inhibition screening results showed that 14 compounds exhibited higher or equivalent inhibitory activity compared to the lead K-5a2 and ETR. Anti-HIV-1 activity results indicated that C1N51 displayed the most potent activity (EC50 = 0.01-0.26 µM) against wild-type and a panel of NNRTIs-resistant strains. Moreover, the molecular simulation demonstrated that the newly introduced triazole ring could develop new hydrogen bonds with Lys103 and Pro236, which explained the feasibility of introducing triazole in the tolerant region I of the RT binding pocket.

Is shared decision-making a determinant of polypharmacy in older patients with chronic disease? A cross-sectional study in Hubei Province, China.

BACKGROUND: Shared decision-making(SDM) is recognized as an important means of managing polypharmacy among older people with chronic diseases. However, no studies have quantitatively measured the effect of SDM on polypharmacy. The objective of this study was to compare the impact of SDM and other factors on polypharmacy in inpatients and community patients. Additionally, the study aimed to compare the impact of different decision types on polypharmacy in community patients. METHODS: This is a population-based multicenter retrospective study conducted in Hubei Province, China. A cluster sampling approach was used to recruit 536 chronic disease inpatients from March to April 2019, and 849 community patients were recruited from April to June 2021. Propensity score weighting was used to control the confounding variables and determine the net effect of SDM on polypharmacy. RESULTS: Among the 536 hospitalized patients, the prevalence of polypharmacy was 56.3%. A high level of SDM was significantly associated with a lower risk of polypharmacy. Patients with chronic illnesses aged 76 years and older and with an annual family income of 24,001-36,000 yuan were associated with a lower likelihood of polypharmacy (p < 0.05). Multimorbidity was often accompanied by the occurrence of multiple medication use. Among 849 community patients, the prevalence of polypharmacy was 21.8%. Among types of decision-making, informed and paternalistic decision-making showed a higher likelihood of polypharmacy compared with shared decision-making (P < 0.05). Male, older patients over 76 years of age, urban residents, annual household income of 12,001-24,000 yuan, and multimorbidity were associated with higher likelihood of polypharmacy (P < 0.05). Patients with an annual household income of 24,001-36,000 yuan, 36,001 yuan or more, and good medication compliance showed a lower likelihood of polypharmacy (P < 0.05). CONCLUSIONS: The prevalence of polypharmacy is high among China's older population with chronic disease who should be paid more atthention by the healthcare providers. Additionaly, encouraging the patients' attendance in SDM, reducing paternalistic and informed decision-making during prescribing, improving patient medication compliance, and increasing the promotion and guidance of rational medication use for patients are essential to reduce polypharmacy in Chinese chronic disease patients.

Analysis of factors that promote the participation of patients with chronic diseases in shared decision making on medication: a cross-sectional survey in Hubei Province, China.

BACKGROUND: Shared decision making (SDM) improves the health status of patients with chronic diseases, especially in the condition of poly-medicated patients. This study aims to find the factors associated with participation of patients with chronic diseases in SDM on medication. METHODS: A total of 1,196 patients with chronic diseases were selected in Hubei Province of China using cluster sampling methods. The random forest method was applied to rank the importance of independent variables by Mean Decrease Gini and out-of- bag (OOB) curve. Multivariate logistic regression was used to explore the independent variables' effect direction and relative hazard. RESULTS: In this study, 5.18% of patients used patient-directed decision making (PDM, a decision-making model led by patients), 37.79% of patients used SDM (a collaborative decision-making model by patients and doctors), and 57.02% of patients used doctor-directed decision making (DDM, or paternalistic decision making, a decision-making model led by doctors). The random forest analysis demonstrated that the top 5 important factors were age, education, exercise, disease course, and medication knowledge. The OOB curve showed that the error rate reached minimum when top 5 variables in importance ranking composed an optimal variable combination. In multivariate logistic regression, we chose SDM as a reference group, and identified medication knowledge (OR = 2.737, 95%CI = 1.524 ~ 4.916) as the influencing factor between PDM and SDM. Meanwhile, the influencing factors between DDM and SDM were age (OR = 0.636, 95%CI = 0.439 ~ 0.921), education (OR = 1.536, 95%CI = 1.122 ~ 2.103), exercise (OR = 1.443, 95%CI = 1.109 ~ 1.877), disease course (OR = 0.750, 95%CI = 0.584 ~ 0.964), and medication knowledge (OR = 1.446, 95%CI = 1.120 ~ 1.867). CONCLUSION: Most Chinese patients with chronic diseases used DDM during their medication decision-making, and some patients used PDM and SDM. The participation in SDM should be taken seriously among elderly patients with lower education levels. The SDM promotion should focus on transformation of patients' traditional perception and enhance their medication knowledge.

Anterior column realignment via a minimally invasive hybrid approach in adult spinal deformity surgery: a short-term retrospective study.

BACKGROUND: Anterior column realignment (ACR) is a novel surgical method for correcting spinal sagittal balance. meanwhile, oblique lumbar interbody fusion (OLIF) and anterior lumbar interbody fusion (ALIF) are considered minimally invasive surgical methods through natural anatomical space. This study aimed to explore the corrective effects and clinical outcomes of OLIF or ALIF combined with ACR technology in patients with adult spinal deformity (ASD). METHODS: We retrospectively analyzed patients with sagittal imbalance who received OLIF and/or ALIF and ACR treatment from 2018 to 2021. Surgical time and intraoperative bleeding volume are recorded, the corrective effect is determined by the intervertebral space angle (IVA), lumbar lordosis (LL), the sagittal vertical axis (SVA), clinical outcome is evaluated by preoperative and final follow-up visual analog pain score (VAS), Japanese orthopedic association scores (JOA) and complications. RESULTS: Sixty-four patients were enrolled in the study, average age of 65.1(range, 47-82) years. All patients completed 173 fusion segments, for 150 segments of ACR surgery. The operation time of ALIF-ACR was 50.4 ± 22.1 min; The intraoperative bleeding volume was 50.2 ± 23.6 ml. The operation time and intraoperative bleeding volume of single-segment OLIF-ACR was 66.2 ± 19.4 min and 70.2 ± 31.6 ml. At the follow-up of 6 months after surgery, the intervertebral space angle correction for OLIF-ACR and ALIF-ACR is 9.2° and 12.2°, the preoperative and postoperative lumbar lordosis were 16.7° ± 6.4°and 47.1° ± 3.6° (p < 0.001), VAS and JOA scores were improved from 6.8 to 1.8 and 7.8 to 22.1 respectively, statistically significant differences were observed in these parameters. The incidence of surgical related complications is 29.69%, but without serious complications. CONCLUSION: ACR via a minimally invasive hybrid approach for ASD has significant advantages in restoring local intervertebral space angulation and correcting the overall sagittal balance. Simultaneously, it can achieve good clinical outcomes and fewer surgical complications.

Risk factors for the accuracy of the initial diagnosis of malaria cases in China: a decision-tree modelling approach.

BACKGROUND: Early accurate diagnosis and risk assessment for malaria are crucial for improving patients' terminal prognosis and preventing them from progressing to a severe or critical stage. This study aims to describe the accuracy of the initial diagnosis of malaria cases with different characteristics and the factors that affect the accuracy in the context of the agenda for a world free of malaria. METHODS: A retrospective study was conducted on 494 patients admitted to hospitals with a diagnosis of malaria from January 2014 through December 2016. Descriptive statistics were calculated, and decision tree analysis was performed to predict the probability of patients who may be misdiagnosed. RESULTS: Of the 494 patients included in this study, the proportions of patients seeking care in county-level, prefecture-level and provincial-level hospitals were 27.5% (n = 136), 26.3% (n = 130) and 8.3% (n = 41), respectively; the proportions of patients seeking care in clinic, township health centre and Centres for Disease Control and Prevention were 25.9% (n = 128), 4.1% (n = 20), and 7.9% (n = 39), respectively. Nearly 60% of malaria patients were misdiagnosed on their first visit, and 18.8% had complications. The median time from onset to the first visit was 2 days (IQR: 0-3 days), and the median time from the first visit to diagnosis was 3 days (IQR: 0-4 days). The decision tree classification of malaria patients being misdiagnosed consisted of six categorical variables: healthcare facilities for the initial diagnosis, time interval between onset and initial diagnosis, region, residence type, insurance status, and age. CONCLUSIONS: Insufficient diagnostic capacity of healthcare facilities with lower administrative levels for the first visit was the most important risk factor in misdiagnosing patients. To reduce diagnostic errors, clinicians, government decision-makers and communities should consider strengthening the primary care facilities, the time interval between onset and initial diagnosis, residence type, and health insurance status.

Hidden blood loss of minimally invasive hybrid lumbar interbody fusion: an analysis of influencing factors.

BACKGROUND: Lumbar interbody fusion(LIF) is the leading way to treat Lumbar Degenerative Diseases(LDD). At present, there is a lack of research on the influencing factors of hidden blood loss in minimally invasive hybrid lumbar interbody fusion. This study comprehensively explores the definite factors affecting the hidden blood loss in minimally invasive hybrid lumbar interbody fusion. MATERIALS AND METHODS: One hundred patients with Lumbar degenerative diseases who underwent minimally invasive hybrid lumbar interbody fusion in our center were included. Demographics, laboratory data, surgical data, and radiographic data were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multi-factor linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: We reviewed and collected 100 patients who underwent minimally invasive hybrid approach, mean age 65 ± 10 years, male: female 37:63; 17 patients of diabetes and 83 patients of non-diabetes; Total blood loss was 645.59 ± 376.37 ml, hidden blood loss was 421.39 ± 337.45 ml, the hidden blood loss percentage was 57 ± 26%. Results from the multi-factorial linear regression model: Diabetes (p < 0.05), hypertension (p < 0.05), psoas thickness (p < 0.05) and dorsal extensor group thickness (p < 0.05) were potential risk factors for postoperative hidden blood loss. CONCLUSION: Although minimally invasive hybrid approach is minimally invasive surgery, there is still a significant amount of hidden blood loss. There is a greater risk of blood loss in diabetes, hypertension and preoperative MRI assessment of thickness of the psoas, thickness of the dorsal extensor group.

Correction: Health Perceptions and Misconceptions Regarding COVID-19 in China: Online Survey Study.

[This corrects the article DOI: 10.2196/21099.].

Associations between short-term exposure of PM2.5 constituents and hospital admissions of cardiovascular diseases among 18 major Chinese cities.

Previous studies showed different risk effects on exposure of fine particulate matter (PM2.5) mass for cardiovascular disease (CVD) globally, which is likely due to different constituents of PM2.5. This study aimed to investigate the association between short-term exposure of PM2.5 constituents and hospital admissions of CVD. Daily counts of city-specific hospital admissions for CVD in 18 cities in China between 2014 and 2017 were extracted from the national Urban Employee Basic Medical Insurance database and the Beijing Municipal Commission of Health and Family Planning Information Center database. Directly measured PM2.5 constituents, including ions and polycyclic aromatic hydrocarbons, were collected by the Chinese Environmental Public Health Tracking system. We used the time-stratified case-crossover design to estimate the association between PM2.5 constituents and hospital admissions of CVD. Concentrations of ions accounted for the majority of the detected constituents. Excess risk (ER) of average ions concentrations for CVD was highest as 2.30% (95% CI: 1.62-2.99%) for NH4+, whose major sources are residential and agricultural emissions. This was followed by 1.85% (1.30-2.41%) for NO3- (generally from vehicles), 0.95% (0.28-1.63%) for SO42- (often from fossil fuel burning) respectively. The association for ions were generally consistent with ischemic heart disease (IHD) and ischemic stroke, e.g., NH4+ was associated with IHD (2.50%; 1.52-3.48%) and ischemic stroke (1.77%; 0.65-2.9%). For polycyclic aromatic hydrocarbons (PAHs), mainly from coal and vehicle-related oil combustion, the constituents were all associated with ischemic stroke but not for IHD. The ER for ischemic stroke was highest at 1.69% (0.99-2.39%) for indeno (123-cd) pyrene. Thus, in terms of the subtypes of CVD, the risks of hospital admissions varied with exposure to different PM2.5 constituents. Exposed to NH4+ had the highest risk to IHD and ischemic stroke, whereas PAHs were predominately associated with ischemic stroke only.

Efficient Aggregate Queries on Location Data with Confidentiality.

Location data have great value for facility location selection. Due to the privacy issues of both location data and user identities, a location service provider can not hand over the private location data to a business or a third party for analysis or reveal the location data for jointly running data analysis with a business. In this paper, we propose a newly constructed PSI filter that can help the two parties privately find the data corresponding to the items in the intersection without any computations and, subsequently, we give the PSI filter generation protocol. We utilize it to construct three types of aggregate protocols for facility location selection with confidentiality. Then we propose a ciphertext matrix compressing method, making one block of cipher contain lots of plaintext data while keeping the homomorphic property valid. This method can efficiently further reduce the computation/communication cost of the query process-the improved query protocol utilizing the ciphertext matrix compressing method is given followed. We show the correctness and privacy of the proposed query protocols. The theoretical analysis of computation/communication overhead shows that our proposed query protocols are efficient both in computation and communication and the experimental results of the efficiency tests show the practicality of the protocols.

Identification of Boronate-Containing Diarylpyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.

In this study, privileged boronic acid ester was introduced into the right wing of etravirine (ETR) to obtain a series of novel boronate-containing derivatives. These newly synthesized derivatives were evaluated for their anti-HIV potency in MT-4 cells using the MTT method, and their inhibitory activity to HIV-1 reverse transcriptase (RT) was assayed by the ELISA method. Most of the synthesized compounds displayed promising antiviral activity against the wild-type and a wide range of HIV-1 mutant strains. In particular, 4a exhibited the most potent activity against the wild-type and a panel of single mutations (L100I, K103N, Y181C, and E138K) with EC50 values ranging from 0.005 to 0.648 µM, which were much superior to those of nevirapine (EC50 = 0.151 µM). Moreover, 4b turned out to be an effective inhibitor against the double-mutant strains F227L + V106A and RES056 with EC50 values of 3.21 and 2.30 µM, respectively. RT inhibition activity and molecular docking were also investigated.

Dual-Channel Logic Gates Operating on the Chemopalette ssDNA-Ag NCs/GO Nanocomposites.

In this work, we demonstrate that the emission wavelength and intensity of silver nanoclusters (Ag NCs) can be facilely tuned by the configuration transformation from the adsorption of Ag NCs to the graphene oxide (GO) surface to the desorption of Ag NCs from GO. Bicolor Ag NCs tethering the complementary sequence of influenza A virus genes are prepared, named green-emitting G-Ag NCs-CH5N1 (530 nm) and red-emitting R-Ag NCs-CH1N1 (589 nm). As for the high affinity of the complementary fragment of genes to GO, the adsorption of Ag NCs to GO leads to the formation of G-Ag NCs-CH5N1/GO and R-Ag NCs-CH1N1/GO nanocomposites, leading to fluorescent quenching due to energy transfer. By conjugating complementary sequences as capturing probes for targets, the formation of genes/Ag NC duplex-stranded structures results in the desorption of Ag NCs from GO, activating the fluorescence signal. More interestingly, compared with sole single-stranded DNA-templated fluorescent Ag NCs (ssDNA-Ag NCs), the activatable emission wavelength of the G-Ag NCs-CH5N1/H5N1 complex exhibits a notable red shift (555 nm) with a 49% recovery rate, while that of the R-Ag NCs-CH1N1/H1N1 complex shows a distinct blue shift (569 nm) with a 200% recovery rate. Via target-responsive configuration transformation of Ag NCs/GO hybrid materials, the emission wavelength and intensity of Ag NCs are effectively regulated. Based on the output changes according to different input combinations, novel dual-channel logic gates for multiplex simultaneous detection are developed by using the tunable color and intensity of ssDNA-Ag NCs. Our observation may open a new path for multiplex analysis in a facile and rapid way combining the logic gate strategy.

Target-Activating and Toehold Displacement Ag NCs/GO Biosensor-Mediating Signal Shift and Enhancement for Simultaneous Multiple Detection.

Herein, we demonstrate that a new multicolor silver nanoclusters/graphene oxide (Ag NCs/GO) hybrid material, upon target response, undergoes a configuration transformation, based on entropy-driven enzyme-free toehold-mediated strand displacement reaction, achieving emission shift and enhancement. To realize the aim above, two different synthesis routes (route I and II) of synthesizing fluorescent Ag NCs for constructing toehold displacement Ag NCs/GO biosensor is designed and performed. Influenza A virus subtype genes (H1N1 and H5N1) as a model can efficiently initiate the operation of entropy-driven displacement reaction, resulting in activatable fluorescence. Red-emitting and green-emitting Ag NCs tethering the complementary sequence of H1N1 (pDNA1) and H5N1 (pDNA2) are indirectly immobilized on GO surface through binding with capture DNA (cDNA1 and cDNA2), respectively, forming multicolor pDNA-Ag NCs/GO nanohybrid materials. However, they do not exhibit nearly fluorescence signals attributed to energy transfer from donor Ag NCs to acceptor GO. Upon adding targets H1N1 and H5N1 (tDNA1 and tDNA2), pDNA1-Ag NCs and pDNA2-Ag NCs detach from GO, based on toehold-mediated strand displacement reaction, which interferes the energy transfer and leads to significant fluorescence enhancement. More interestingly, the activatable process is accompanied by remarkable hypsochromic shift (19 nm) or bathochromic shift (21 nm) emission with quite high fluorescence recovery rates (823.35% and 693.62%). Therefore, based on these phenomena, a novel multiple approach has been developed with the assistance of toehold displacement and Ag NCs/GO nanohybrid materials. As for the remarkable emission recovery and multichannel signal, the proposed approach displays the promising application prospect in accurate diagnosis and treatment.

Design, synthesis, and antiviral evaluation of novel piperidine-substituted arylpyrimidines as HIV-1 NNRTIs by exploring the hydrophobic channel of NNIBP.

Herein, alkenylpiperidine and alkynylpiperidine moieties were introduced into the left wing of DAPYs (diarylpyrimidines) to explore the new site of the NNIBP (non-nucleoside inhibitor binding pocket) protein-solvent interface region via the structure-based drug design strategy. All the synthesized compounds displayed nanomolar to submicromolar activity against WT (wild-type) HIV-1. Among all, compound FT1 (EC50 = 19 nM) was found to be the most active molecule, which is better than NVP (EC50 = 0.10 µM). In addition, most of the compounds displayed micromolar activity against K103N and E138K mutant strains, while FT1 (EC50(K103N) = 50 nM, EC50(E138K) = 0.19 µM) still has the most effective activity. The molecular dynamics simulation studies revealed that the presence of pyridine moiety of FT1 was essential and played a significant role in its binding with RT (reverse transcriptase).

Impact of child's migration on health status and health care utilization of older parents with chronic diseases left behind in China.

BACKGROUND: Adult child are used to taking the responsibility of taking care of their older parents in Chinese culture. However, the migration of adult child is not uncommon now in the context of urbanization in China. The purpose of this study is to explore the impact of child's migration on health status and health care utilization of older parents with chronic diseases left behind. METHODS: The data of the 2015 nationally representative longitudinal survey of the aged population in China were used in this study. Binary logistic regression was used to evaluate the impact of adult child's migration on health status and health care utilization of older parents with chronic diseases left behind. RESULTS: About a quarter of the respondents (25.5%) had at least one migrant child. Most of the respondents (86.6%) rated their health as poor, and 42.0% of them suffered from physical limitations. Nearly half of the respondents (45.0%) had depressive symptoms, but the vast majority (88.2%) were generally satisfied with their lives. Only a quarter of the respondents received outpatient treatment in the past month while only one fifth of them received inpatient visits in the past year. After controlling for other demographic and socioeconomic variables, it was found in this study that those who with migrant child were more likely to report poor self-rated health (OR = 1.26; 95% CI 1.01-1.58), not satisfied with general life (OR = 1.28; 95% CI 1.03-1.59) and seek outpatient visits (OR = 1.22; 95% CI 1.03-1.43) than those who without migrant child. CONCLUSION: Our study found that there is a negative association between migration of adult child and physical health, mental health and health care utilization of older parents with chronic diseases left behind, which means a comprehensive effect on their health status. Further health policies should focus on improving the well-being of older parents with chronic diseases left behind.