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Highlights Exploiting single-atom catalytic activation and targeted adsorption properties, Ni single-atom active sites based on N, C coordination are constructed on the surface of two-dimensional MXene nanosheets (Ni–N–C/Ti3C2Tx), enabling highly sensitive and selective NH3 gas detection. The catalytic activation effect of Ni–N–C/Ti3C2Tx effectively reduces the Gibbs free energy of the sensing elemental reaction, while its electronic structure promotes the spill-over effect of reactive oxygen species at the gas–solid interface. An end-sealing passivation strategy utilizing a conjugated hydrogen bond network of the conductive polymer was employed on MXene-based flexible electrodes, effectively mitigating the oxidative degradation of MXene-based gas sensors.

Abstract Real-time and accurate biomarker detection is highly desired in point-of-care diagnosis, food freshness monitoring, and hazardous leakage warning. However, achieving such an objective with existing technologies is still challenging. Herein, we demonstrate a wireless inductor-capacitor (LC) chemical sensor based on platinum-doped partially deprotonated-polypyrrole (Pt-PPy+ and PPy0) for real-time and accurate ammonia (NH3) detection. With the chemically wide-range tunability of PPy in conductivity to modulate the impedance, the LC sensor exhibits an up-to-180% improvement in return loss (S11). The Pt-PPy+ and PPy0 shows the p-type semiconductor nature with greatly-manifested adsorption-charge transfer dynamics toward NH3, leading to an unprecedented NH3 sensing range. The S11 and frequency of the Pt-PPy+ and PPy0-based sensor exhibit discriminative response behaviors to humidity and NH3, enabling the without-external-calibration compensation and accurate NH3 detection. A portable system combining the proposed wireless chemical sensor and a handheld instrument is validated, which aids in rationalizing strategies for individuals toward various scenarios.

Abstract Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen‐induced sterile inflammation regulates EH remains unclear. Here, a single‐cell RNA‐Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1β and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell–macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA‐Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1Tyr380. This event activates downstream activator protein 1 (AP‐1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial‐specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol‐driven acute inflammation to macrophage‐amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen‐related diseases.

Objectives: While the decision of abortion is undeniably complex, there are situations where it becomes a necessary choice. In such circumstances, a secure abortion procedure is essential to safeguard the physical and mental well-being of women. A uterine direct visualization system was designed to fulfill the requirements and this study undertook an assessment of the system's safety and effectiveness within a medical facility setting. Materials and methods: Induced abortion requested women in 17 institutions across the country between December 2016 and February 2017 were enrolled. Subjects were separated to the study and control group randomly. Induced abortion was conducted by a uterine direct visualization system and an ultrasound-guided system in the study and control group, respectively. The clinical indexes collected during intra- and post-procedures were analyzed and compared between groups. Results: Overall, 392 and 339 subjects were included in the study and control group, respectively. The baseline demographic and clinical characteristics were similar between two groups. Subjects in the study group had significant smaller number of uterine cavity entry (p

Parkinson's disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins, including α-synuclein, amyloid-β, and tau, in addition to the impaired elimination of these neurotoxic protein. Atypical parkinsonism, which has the same clinical presentation and neuropathology as Parkinson's disease, expands the disease landscape within the continuum of Parkinson's disease and related disorders. The glymphatic system is a waste clearance system in the brain, which is responsible for eliminating the neurotoxic proteins from the interstitial fluid. Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease, as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage. Therefore, impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration. Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson's disease and related disorders; however, many unanswered questions remain. This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson's disease and related disorders. The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins, including loss of polarization of aquaporin-4 in astrocytic endfeet, sleep and circadian rhythms, neuroinflammation, astrogliosis, and gliosis. This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson's disease and related disorders, and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

Abstract Prodrug photolysis enables spatiotemporal control of drug release at the desired lesions. For photoactivated therapy, near-infrared (NIR) light is preferable due to its deep tissue penetration and low phototoxicity. However, most of the photocleavable groups cannot be directly activated by NIR light. Here, we report a upconversion-like process via only one step of energy transfer for NIR light-triggered prodrug photolysis. We utilize a photosensitizer (PS) that can be activated via singlet-triplet (S-T) absorption and achieve photolysis of boron-dipyrromethene (BODIPY)-based prodrugs via triplet-triplet energy transfer. Using the strategy, NIR light can achieve green light-responsive photolysis with a single-photon process. A wide range of drugs and bioactive molecules are designed and demonstrated to be released under low-irradiance NIR light (100 mW/cm2, 5 min) with high yields (up to 87%). Moreover, a micellar nanosystem encapsulating both PS and prodrug is developed to demonstrate the practicality of our strategy in normoxia aqueous environment for cancer therapy. This study may advance the development of photocleavable prodrugs and photoresponsive drug delivery systems for photo-activated therapy.

Fire blight, caused by the Gram-negative bacterium Erwinia amylovora, poses a substantial threat to pome fruit production worldwide. Despite existing control strategies, a pressing need remains for sustainable and environmentally friendly fire blight management. Myxobacteria, renowned for their predatory behavior and potent enzymes, emerge as a groundbreaking biocontrol approach with significant potential. Here, we report the biocontrol potential of a novel Myxococcus fulvus WCH05, against E. amylovora. Using various in vitro and planta assays, we demonstrated the multifaceted biocontrol abilities of strain WCH05. In plate predation assays, strain WCH05 exhibited not only strong predation against E. amylovora but also broad-spectrum activities against other plant pathogenic bacteria. Pre-treatment with strain WCH05 significantly decreased pear blossom blight incidence in detached inflorescence assays, achieving a controlled efficacy of 76.02% that rivaled the antibiotic streptomycin (79.79%). In greenhouse trials, strain WCH05 effectively reduced the wilting rate and disease index in young pear seedlings, exhibiting both protective (73.68%) and curative (68.66%) control. Further investigation revealed that the biocontrol activity of strain WCH05 relies on both direct contact and extracellular enzyme secretion. While cell extracts lacked inhibitory activity, ammonium sulfate-precipitated secreted proteins displayed potent lytic activity against E. amylovora. Substrate spectrum analysis identified peptidases, lipases, and glycosidases among the secreted enzymes, suggesting their potential roles in pathogen degradation and biocontrol efficacy. This study presents the first evidence of Myxococcus fulvus WCH05 as a biocontrol agent against fire blight. Its potent predatory abilities and enzymatic arsenal highlight its potential for sustainable disease management in pome fruit production. Future research will focus on identifying and characterizing specific lytic enzymes and optimizing strain WCH05 application strategies for field efficacy.

ABSTRACT: Excess abdominal fat reduces carcass yield and feed conversion ratio, thereby resulting in significant economic losses in the poultry industry. Our previous study demonstrated that dietary addition of folic acid reduced fat deposition and changed gut microbiota and short-chain fatty acid. However, whether folic acid regulating abdominal fat deposition was mediated by gut microbiota was unclear. A total of 210 one-day-old broiler chickens were divided into 3 groups including the control (CON), folic acid (FA), and fecal microbiota transplantation (FMT) groups. From 14th day, broiler chickens in CON and FA groups were given perfusion administration with 1 mL diluent daily, while 1 mL fecal microbiota transplantation suspension from FA group prepared before was perfusion in FMT group receiving control diets. The result showed that abdominal fat percentage was significantly lower in FA and FMT groups when compared with CON group (P < 0.05). Morphology analysis revealed that the villus height of jejunum and ileum were significantly higher in FMT group (P < 0.05), and the villus height of jejunum was also significantly higher in FA group (P < 0.05), while the diameter and cross-sectional area (CSA) of adipocytes were significantly decreased in FA and FMT groups when compared with CON group (P < 0.05). Western blot results indicated that the expression levels of FOXO1 and PLIN1 in FMT group were significantly increased (P < 0.05), whereas the expression levels of PPARγ, C/EBPα, and FABP4 were significantly decreased (P < 0.05). Additionally, the Chao1, Observed-species, Shannon and Simpson indexes in FA and FMT groups were significantly higher (P < 0.05), but the microbiota were similar between FMT and FA groups (P < 0.05). LEfSe analysis determined that Lactobacillus, Clostridium and Dehalobacterium were found to be predominant in FA group, while Oscillospira, Shigella, and Streptococcus were the dominant microflora in FMT group. Furthermore, these cecal microbiota were mostly involved in infectious disease, cellular community prokaryotes, cell motility and signal transduction in FA group (P < 0.05), whereas functional capacities involved in signal transduction, cell motility, infectious disease and environment adaptation were enriched significantly of cecal microbiota in FMT group (P < 0.05). In summary, both fecal microbiota transplantation from the broiler chickens of dietary added folic acid and dietary folic acid addition effectively reduced abdominal fat deposition, indicating that the regulatory effect of folic acid on abdominal fat deposition was mediated partly by gut microbiota in broiler chickens.

Important tick-borne diseases include spotted fever group Rickettsia (SFGR), Anaplasma, and Ehrlichia, which cause harm to animal and human health. Ixodidae are the primary vectors of these pathogens. We aimed to analyze the prevalence and genetic diversity of SFGR, Anaplasma, and Ehrlichia species in the Ixodidae in Shaanxi Province, China. Herein, 1,113 adult Ixodidae ticks were collected from domestic cattle and goats, and detected using nested PCR. A total of four Ixodidae species were collected and Ca. R. jingxinensis (20.58%, 229/1113), A. bovis (3.05%, 34/1113), A. capra (3.32%, 37/1113), A. marginale (0.18%, 2/1113), E. sp. Yonaguni138 (0.18%, 2/1113), and a potent novel Ehrlichia species named E. sp. Baoji96 (0.09%, 1/1113) were detected. A. marginale was detected for the first time in Rhipicephalus microplus. E. sp. Baoji96 was closely related to E. chaffeensis and was first identified in Haemaphysalis longicornis. In addition, co-infection with two Rickettsiales pathogens within an individual tick was detected in 10 (1.54%) ticks. This study provides a reference for the formulation of biological control strategies for ticks and tick-borne diseases in Shaanxi Province, and could lead to an improved control effect.

Abstract Background This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. Methods A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. Results 4SCAR-T cells expanded for 1–3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. Conclusion Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. Trial registration ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.

Abstract The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

Beta-amyloid protein (Aβ) is one of the most important pathogenic factors of Alzheimer’s disease (AD). N-linoleyltyrosine (NITyr) was synthesized in our laboratory and exerted neuroprotective effects in APP/PS1 transgenic mice in previous reports. In this study, the neuroprotective effects and mechanisms of NITyr were evaluated in Aβ1–40-treated primary cortical neurons for the first time in vitro. NITyr treatment attenuated cytotoxicity induced by Aβ1–40, and the best effect of NITyr was observed at 1 μmol/L. NITyr treatment increased the BDNF protein expression and the ratio of p-CREB/CREB, but weakened the Caspase-3 protein expression. Meanwhile, NITyr enhanced the expressions of autophagy-related proteins (LC3-II, Beclin-1, ATG5 and ATG13). The autophagy inhibitor 3-methyladenine (3MA) reversed the effects of NITyr on cell viability and the protein expressions of neuron-related proteins, including BDNF, p-CREB and Caspase-3. The CB2 receptor antagonist AM630 weakened the neuroprotective effects of NITyr and the autophagy-related protein expression (LC3-II, Beclin-1, ATG5 and ATG13). Moreover, NITyr significantly increased the expressions of p-AMPK, p-mTOR and p-ULK1, but not p-p38. AM630 ablated the above phenomenon. Therefore, NITyr protected the neurons against Aβ1–40-induced cytotoxicity by inducing autophagy, which involved the CB2/AMPK/mTOR/ULK1 pathway.

IntroductionGreen finance plays a crucial role in driving sustainable development and has the potential to effectively reduce pollution emissions, thereby positively impacting the environment. However, in the agricultural sector, China, unlike developed countries, primarily relies on a small-peasant economy, and the green financial system is not well-developed. As a result, the specific emission reduction effects and mechanisms of green finance on agricultural non-point source pollution (ANSP) remain unclear. The objective of our research is to explore the internal mechanisms through which green finance influences ANSP, with the aim of providing valuable policy insights to the government and promoting the green transformation of agriculture for enhanced food security.MethodsThis study employs an empirical analysis of green finance on ANSP using provincial panel data from China spanning the years 2005 to 2020. By utilizing robust data and applying empirical analysis, we can derive scientifically credible conclusions. We introduce a relative indicator to assess the trend of ANSP and investigate the pathways through which green finance operates using heterogeneity analysis, intermediary effect evaluation, and threshold effect analysis.Results and DiscussionThe empirical findings reveal the following insights: (1) While green finance demonstrates a significant reduction effect on ANSP, this effect varies across different regions. Specifically, the impact of green finance on ANSP reduction is more pronounced in areas characterized by strong comprehensive agricultural strength, high levels of economic development, and predominantly focused on plantation agriculture. (2) From a mechanistic standpoint, green finance substantially diminishes ANSP by facilitating agricultural scaling and promoting the adoption of green technologies. (3) The threshold effect analysis demonstrates that the mitigation effect of green finance on ANSP exhibits non-linear characteristics, with a double threshold effect observed. As the level of green finance development increases, the mitigation effect is further enhanced.ConclusionIn conclusion, the appropriate implementation of green finance can effectively enhance the agricultural environment and ensure food security. Considering the heterogeneity of the role of green finance and the presence of threshold values, it is crucial for the government to tailor green finance policies according to local conditions. This research not only expands on previous studies but also offers valuable insights for the government in formulating green finance policies. Furthermore, it provides a viable pathway for reducing ANSP while serving as a reference for other developing countries aiming to establish green agriculture and sustain food system security.

The quantitative evaluation of the coupling coordination degree (CCD) between the regional economy and eco-environment systems is of great importance for the realization of sustainable development goals, which could identify economic or eco-environmental cold areas. To date, traditional evaluation frameworks mainly include the indicator system construction based on statistical data, which seldom utilize the geo-spatiotemporal datasets. Hence, this study aimed to evaluate the CCD change trend of the Yangtze River Delta (YRD) and explore the relationship between the CCD, economy, and eco-environment on the county scale. In this study, YRD was selected as the study area to evaluate its level of CCD at different periods, and then the nighttime difference index (NTDI) and eco-environmental comprehensive evaluation index (ECEI) were calculated to represent the difference in the development of the regional economy and the eco-environmental quality (EEQ). The CCD between the two systems was then calculated and analyzed using global, local, and Geary’s C spatial autocorrelation indicators, in addition to change trend methods. The main findings showed that: (1) During the period 2000–2020, the economic system in YRD showed a continuously upward trend (0.0487 a−1), with average NTDI values of 0.2308, 0.2964, 0.3223, 0.3971, and 0.4239, respectively. In spatial terms, the economy system showed a distribution of “high in the east and low in the west”. (2) YRD’s EEQ indicated a gradual upward trend (from 0.3590 in 2000 to 0.3970 in 2020), with a change trend value of 0.0020 a−1. Spatially, the regions with high ECEI were mainly located in southwestern counties. (3) In the past 20 years, the CCD between economic and eco-environment systems showed an increased change trend, with a change trend value of 0.0302 a−1. The average CCD values for the five periods were 0.3992, 0.4745, 0.4633, 0.5012, and 0.5369. The overall level of CCD improved from “moderate incoordination” to “low coordination”. (4) Both NTDI and ECEI indexes have a positive effect on the improvement of regional CCD. However, the contribution of NTDI is a little higher than that of ECEI.

Abstract Real-time rapid detection of toxic gases at room temperature is particularly important for public health and environmental monitoring. Gas sensors based on conventional bulk materials often suffer from their poor surface-sensitive sites, leading to a very low gas adsorption ability. Moreover, the charge transportation efficiency is usually inhibited by the low defect density of surface-sensitive area than that in the interior. In this work, a gas sensing structure model based on CuS quantum dots/Bi2S3 nanosheets (CuS QDs/Bi2S3 NSs) inspired by artificial neuron network is constructed. Simulation analysis by density functional calculation revealed that CuS QDs and Bi2S3 NSs can be used as the main adsorption sites and charge transport pathways, respectively. Thus, the high-sensitivity sensing of NO2 can be realized by designing the artificial neuron-like sensor. The experimental results showed that the CuS QDs with a size of about 8 nm are highly adsorbable, which can enhance the NO2 sensitivity due to the rich sensitive sites and quantum size effect. The Bi2S3 NSs can be used as a charge transfer network channel to achieve efficient charge collection and transmission. The neuron-like sensor that simulates biological smell shows a significantly enhanced response value (3.4), excellent responsiveness (18 s) and recovery rate (338 s), low theoretical detection limit of 78 ppb, and excellent selectivity for NO2. Furthermore, the developed wearable device can also realize the visual detection of NO2 through real-time signal changes.

Abstract Background Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states. Results Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo. Conclusions This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis. Graphical Abstract

Abstract Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta = 8.36 × 10−8, OR = 1.29; rs7259428, 19q12, ZNF536, P meta = 7.58 × 10−8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta = 1.95 × 10−8; rs2414487, 15q21.3, LOC145783, P meta = 4.53 × 10−9; rs2106525, 7q31.1, MDFIC, P meta = 6.24 × 10−9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Background: Exercise can modulate gut microbiota and lower the risk of cardiovascular disease (CVD). However, the association between exercise-induced changes in gut microbiota and CVD risk have not been investigated.Objective: This study determined the effects of exercise training on CVD risk and gut microbiota in physically active elderly women and whether exercise-induced gut microbiota changes were associated with CVD risk.Methods: An 8-week randomized controlled trial was conducted with 14 elderly women assigned to exercise group (n = 8) or control group (n = 6). Physical function, sarcopenic obesity, and metabolic syndrome were evaluated as components of CVD risk. Gut microbiota composition was determined using 16S rRNA gene sequencing. Repeated-measures analysis of variance was used to examine intra-group and inter-group differences.Results: A significant group × time interaction was observed for chair sit-and-reach (F = 8.262, p = 0.014), single-leg standing with eyes closed (F = 7.340, p = 0.019), waist circumference (F = 6.254, p = 0.028), and body fat mass (F = 12.263, p = 0.004), for which the exercise group showed improved trends. The exercise group exhibited significant improvements in skeletal muscle mass (p = 0.041) and fasting blood glucose (p = 0.017). Regarding gut microbiota, a significant interaction was observed for the class Betaproteobacteria (F = 6.822, p = 0.023) and genus Holdemania (F = 4.852, p = 0.048).Conclusion: The 8-week exercise training improved physical function, lowered CVD risk, and modulated relative abundance of gut microbiota associated with CVD in physically active elderly women.

Chinese nouns lack inflection and cannot reflect the quantitative relationship between singular and plural numbers. However, neural processes of picture naming are different from those of words. We assume that Chinese single and plural picture naming is different, and they may involve quantitative processing. Therefore, Experiment 1 was designed by picking picture naming as the task and Chinese as the target language and compared the accuracy, reaction time, and event-related potentials (ERPs) between single and plural picture naming, where two types of pictures were mixed. Although the T-test showed no significant differences in behavioral data, there were differences in ERPs. ERP differences involved two effects: P1 of 160–180 ms and P2 of 220–260 ms in the parietal-occipital lobe. These differences are suggested to reflect the neural differences in quantitative processing. Therefore, Chinese singular and plural picture naming consists of word production and implicit quantitative processing simultaneously. To explore the relationship between the two processings, we added a semantic factor (inanimate vs. animate items) to the quantity factor of Experiment 1 and carried out Experiment 2, with the observation indexes unchanged. There were no significant differences in behavioral data among the four conditions. After variance analysis, ERPs results indicated an interaction between semantic and quantitative factors in the central area at 180–280 ms. In summary, we suggest that Chinese singular and plural picture naming includes two simultaneous neural processing tasks: word production and quantitative processing, which interact in the central area at 180–280 ms.

Abstract Photocleavable prodrugs enable controllable drug delivery to target sites modulated by light irradiation. However, the in vivo utility is usually hindered by their insolubility and inefficient delivery. In this study, we report a simple strategy of co‐assembling boron‐dipyrromethene‐chlorambucil prodrug and near‐infrared dye IR783 to fabricate photoresponsive nanoassemblies, which achieved both high prodrug loading capacity (~99%) and efficient light‐triggered prodrug activation. The incorporated IR783 dye not only stabilized the nanoparticles and contributed tumor targeting as usual, but also exhibited degradation after light irradiation and in‐situ monitoring of nanoparticle dissociation by fluorescent imaging. Systemic administration of the nanoparticles and localized light irradiation at tumor sites enabled monitorable and efficient drug release in vivo. Our results demonstrate that such prodrug‐dye co‐assembled nanomedicine is a promising formulation for photoresponsive drug delivery, which would advance the translation of photoresponsive nanomedicines.

Background: While the grading of intestinal fibrosis is closely related to the therapeutic strategy of patients with Crohn’s disease (CD), it has not yet been well resolved. Mesenteric abnormalities are inextricably linked to intestinal fibrosis. Objectives: We aimed to establish an optimal model for assessing intestinal fibrosis using computed tomography enterography (CTE) and clinical markers. Design: A total of 174 patients with CD between January 2014 and June 2020 were included in this retrospective multicentre study. Methods: All patients underwent CTE within 3 months prior to surgery. Intestinal fibrosis was pathologically scored as non-mild or moderate-to-severe. Selected imaging of the intestinal walls and mesentery and/or clinical factors were used to develop the diagnostic models. The area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the discrimination performance of the models. A decision curve analysis was performed to evaluate the clinical usefulness of the models. Results: One-, two-, and three-variable models were identified as possible diagnostic models. Model 1 [mesenteric creeping fat index (MCFI)], Model 2 (mesenteric oedema and MCFI), and Model 3 (mesenteric oedema, MCFI, and disease duration) were established. The AUCs of Model 1 in training and test cohorts 1 and 2 were 0.799, 0.859, and 0.693, respectively; Model 2 was 0.851, 0.833, and 0.757, respectively; and Model 3 was 0.832, 0.821, and 0.850, respectively. We did not observe any significant difference in diagnostic performance between the training and total test cohorts in any model (all p > 0.05). The decision curves showed that Model 3 had the highest net clinical benefit in test cohort 2. The nomogram of this optimal model was constructed by considering the favourable and robust performance of Model 3. Conclusion: A nomogram integrating mesenteric abnormalities on CTE with a clinical marker was optimal for differentiating between non-mild and moderate-to-severe fibrosis in patients with CD.

PurposeSurgical site infection (SSI) remains one of the most common postoperative complications for patients with abdominal infections. This study aimed at investigating the effectiveness of high-volume normal saline (NS) irrigation in preventing postoperative SSI for patients with abdominal infections.MethodsIn this retrospective before-after clinical study, patients who underwent emergency laparotomy due to abdominal infections between Jan 2015 and Dec 2021 were included consecutively. A cohort of 207 patients with NS irrigation was compared to historical controls. A propensity score matching (PSM) with a 1:1 ratio was performed to reduce potential bias. The primary outcome was the 30-day SSI rate.ResultsIrrigation (n = 207) and control (n = 207) matched patients were statistically identical on baseline characteristics, perioperative, and intraoperative parameters. Irrigation patients had lower overall SSI rates (10.6% vs. 26.1%, p

Abstract Perivascular space (PVS) is associated with neurodegenerative diseases, while its effect on Parkinson’s disease (PD) remains unclear. We aimed to investigate the clinical and neuroimaging significance of PVS in basal ganglia (BG) and midbrain in early-stage PD. We recruited 40 early-stage PD patients and 41 healthy controls (HCs). Both PVS number and volume were calculated to evaluate PVS burden on 7 T magnetic resonance imaging images. We compared PVS burden between PD and HC, and conducted partial correlation analysis between PVS burden and clinical and imaging features. PD patients had a significantly more serious PVS burden in BG and midbrain, and the PVS number in BG was significantly correlated to the PD disease severity and L-dopa equivalent dosage. The fractional anisotropy and mean diffusivity values of certain subcortical nuclei and white matter fibers within or nearby the BG and midbrain were significantly correlated with the ipsilateral PVS burden indexes. Regarding to the midbrain, the difference between bilateral PVS burden was, respectively, correlated to the difference between fiber counts of white fiber tract passing through bilateral substantia nigra in PD. Our study suggests that PVS burden indexes in BG are candidate biomarkers to evaluate PD motor symptom severity and aid in predicting medication dosage. And our findings also highlight the potential correlations between PVS burden and both grey and white matter microstructures.

Objective: Rising cesarean section rates have led to an increase in cesarean scar defects. However, there is no consensus regarding the gold standard for treating cesarean scar defects. This study aims to compare the efficacy of laparoscopy combined with hysteroscopy and hysteroscopy in treating cesarean scar defects. Methods: An electronic search of the MEDLINE, EMBASE, and Clinical Trials.gov databases was conducted in May 2020, utilizing combinations of relevant medical subject headings for “cesarean scar defect”, “laparoscope”, and “hysteroscope”. Reference lists of relevant articles and reviews were hand-searched for additional reports. Observed outcomes included menstruation after surgery, blood loss, operative time, and further fertility. Results: Eight studies with 467 patients were included. The menstruation duration after surgery for the laparoscopy combined with hysteroscopy group and hysteroscopy group was comparable. While the laparoscopy combined with hysteroscopy group trended to have less blood loss (mean difference 49.60, 95% CI: 42.12–57.09, p

Abstract Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC‐II and LCK, which were mainly associated with activities of antigen‐presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7‐H3. Finally, Kaplan‐Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor‐related immune response.

Abstract Background Deep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial. Methods/design We propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand–walk–sit task scores after 3 months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation. Discussion This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future. Trial registration ClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.

Given the limited power of neuropsychological tests, there is a need for a simple, reliable means, such as gait, to identify mild dementia and its subtypes. However, gait characteristics of patients with post-stroke dementia (PSD) and Alzheimer’s disease (AD) are unclear. We sought to describe their gait signatures and to explore gait parameters distinguishing PSD from post-stroke non-dementia (PSND) and patients with AD. We divided 3-month post-stroke patients into PSND and PSD groups based on the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the activity of daily living (ADL). Thirty-one patients with AD and thirty-two healthy controls (HCs) were also recruited. Ten gait parameters in one single and two dual-task gait tests (counting-backward or naming-animals while walking) were compared among the groups, with adjustment for baseline demographic covariates and the MMSE score. The area under the receiver operating characteristic curve (AUC) was used to identify parameters discriminating PSD from individuals with PSND and AD. Patients with PSD and patients with AD showed impaired stride length, velocity, stride time, and cadence while patients with PSD had altered stance and swing phase proportions (all p ≤ 0.01, post hoc). Patients with AD had smaller toe-off (ToA) and heel-to-ground angles (HtA) (p ≤ 0.01) than HCs in dual-task gait tests. Individuals with PSD had a shorter stride length, slower velocity, and altered stance and swing phase percentages in all tests (p ≤ 0.01), but a higher coefficient of variation of stride length (CoVSL) and time (CoVST) only in the naming animals-task gait test (p ≤ 0.001) than individuals with PSND. ToA and HtA in the naming animals-task gait test were smaller in individuals with AD than those with PSD (p ≤ 0.01). Statistical significance persisted after adjusting for demographic covariates, but not for MMSE. The pace and the percentage of stance or swing phase in all tests, CoVST in the dual-task paradigm, and CoVSL only in the naming animals-task gait test (moderate accuracy, AUC > 0.700, p ≤ 0.01) could distinguish PSD from PSND. Furthermore, the ToA and HtA in the naming animals-task gait paradigm discriminated AD from PSD (moderate accuracy, AUC > 0.700, p ≤ 0.01). Thus, specific gait characteristics could allow early identification of PSD and may allow non-invasive discrimination between PSD and AD, or even other subtypes of dementia.

Abstract Retinoblastoma is one of the most severe ocular diseases, of which current chemotherapy is limited to the repetitive intravitreal injections of chemotherapeutics. Systemic drug administration is a less invasive route; however, it is also less efficient for ocular drug delivery because of the existence of blood‐retinal barrier and systemic side effects. Here, a photoresponsive drug release system is reported, which is self‐assembled from photocleavable trigonal small molecules, to achieve light‐triggered intraocular drug accumulation. After intravenous injection of drug‐loaded nanocarriers, green light can trigger the disassembly of the nanocarriers in retinal blood vessels, which leads to intraocular drug release and accumulation to suppress retinoblastoma growth. This proof‐of‐concept study would advance the development of light‐triggered drug release systems for the intravenous treatment of eye diseases.

LIGHT, also termed TNFSF14, has been reported to play a vital role in different tumors. However, its role in glioma remains unknown. This study is aimed at unveiling the characterization of the transcriptional expression profiling of LIGHT in glioma. We selected 301 glioma patients with mRNA microarray data from the CGGA dataset and 697 glioma patients with RNAseq data from the TCGA dataset. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analyses and figure generation were performed with R language. LIGHT expression showed a positive correlation with WHO grade of glioma. LIGHT was significantly increased in mesenchymal molecular subtype. Gene Ontology analysis demonstrated that LIGHT was profoundly involved in immune response. Moreover, LIGHT was found to be synergistic with various immune checkpoint members, especially HVEM, PD1/PD-L1 pathway, TIM3, and B7-H3. To get further understanding of LIGHT-related immune response, we put LIGHT together with seven immune signatures into GSVA and found that LIGHT was particularly correlated with HCK, LCK, and MHC-II in both datasets, suggesting a robust correlation between LIGHT and activities of macrophages, T-cells, and antigen-presenting cells (APCs). Finally, higher LIGHT indicated significantly shorter survival for glioma patients. Cox regression models revealed that LIGHT expression was an independent variable for predicting survival. In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.

Abstract Background Serum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke. Methods This was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. Results A total of 768 patients were finally included in the study and divided into two age groups: a younger group (age

Patients with Parkinson's disease (PD) were often observed with gastrointestinal symptoms, which preceded the onset of motor symptoms. Neuropathology of PD has also been found in the enteric nervous system (ENS). Many studies have reported significant PD-related alterations of gut microbiota. This meta-analysis was performed to evaluate the differences of gut microbiota between patients with PD and healthy controls (HCs) across different geographical regions. We conducted a systematic online search for case-control studies detecting gut microbiota in patients with PD and HCs. Mean difference (MD) and 95% confidence interval (CI) were calculated to access alterations in the abundance of certain microbiota families in PD. Fifteen case-control studies were included in this meta-analysis study. Our results showed significant lower abundance levels of Prevotellaceae (MD = −0.37, 95% CI = −0.62 to −0.11), Faecalibacterium (MD = −0.41, 95% CI: −0.57 to −0.24), and Lachnospiraceae (MD = −0.34, 95% CI = −0.59 to −0.09) in patients with PD compared to HCs. Significant higher abundance level of Bifidobacteriaceae (MD = 0.38, 95%; CI = 0.12 to 0.63), Ruminococcaceae (MD = 0.58, 95% CI = 0.07 to 1.10), Verrucomicrobiaceae (MD = 0.45, 95% CI = 0.21 to 0.69), and Christensenellaceae (MD = 0.20, 95% CI = 0.07 to 0.34) was also found in patients with PD. Thus, shared alterations of certain gut microbiota were detected in patients with PD across different geographical regions. These PD-related gut microbiota dysbiosis might lead to the impairment of short-chain fatty acids (SCFAs) producing process, lipid metabolism, immunoregulatory function, and intestinal permeability, which contribute to the pathogenesis of PD.

In this paper, Clifford-valued fuzzy neural networks with proportional delays, whose leakage term coefficients are also Clifford numbers, are considered. Based on the Banach fixed point theorem and differential inequality technique, we use a direct method to obtain the existence, uniqueness, and global attractivity of pseudo almost periodic solutions for the considered networks. Finally, we provide a numerical example to illustrate the feasibility of our results. Our results are new.

In response to the problems of small working width and low operating efficiency of existing hydraulic scouring lotus root harvesters, a wide-width hydraulic scouring system was designed based on a wide-width self-propelled lotus root harvester. The main parameters of the key components were determined through theoretical analysis of the water flow energy of the hydraulic scouring system pipelines. An experimental study was also carried out on the main factors affecting the working performance of this hydraulic scouring system. Through hydrodynamic simulation tests, the effect of nozzle type and constriction section structure on the turbulence intensity at the nozzle outlet and the pressure loss per unit mass of fluid between the nozzle inlet and outlet sections were compared and analysed. The test yielded conical-cylindrical nozzle geometry parameters for nozzle inlet diameter of 40 mm, shrinkage angle of 30°, nozzle outlet straight section length of 20 mm, nozzle outlet diameter of 16 mm, the nozzle had better flushing performance. Single-factor tests were carried out with nozzle outlet pressure, scouring angle and nozzle height from the mud surface as influencing factors. Based on the optimum effective scour depth, a three-factor, three-level Box–Behnken central combination design test was completed. The primary and secondary factors affecting the effective scouring depth were obtained in the following order: nozzle height from the mud surface, nozzle outlet pressure, and scouring angle. Finally, the performance test of the hydraulic scouring system was completed. Results showed that when the nozzle outlet pressure of 0.30 MPa, the scouring angle of 60° and the nozzle height from the mud surface of 0 mm, the effective scouring depth was 395 mm, the lotus root floating rate was 90% and the damage rate was 5%, which meet the requirements of lotus root harvesting operations.

IntroductionCurrent evidence supporting the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) as a first-line treatment option for malignant biliary obstruction (MBO) is limited. We plan to provide a systematic review and meta-analysis to compare the performance of EUS-BD and endoscopic retrograde cholangiopancreatography-guided biliary drainage (ERCP-BD) as primary palliation of MBO.Methods and analysisRandomised controlled trials evaluating EUS-BD versus ERCP-BD in primary drainage of MBO will be searched in MEDLINE, EMBASE, Web of Science, the Cochrane Library, ClinicalTrials.gov and Google Scholar, from database inception to 31 October 2018. Data on study design, participant characteristics, intervention details and outcomes will be extracted. Primary outcomes to be assessed are technical and clinical success. Secondary outcomes include adverse events, stent patency, stent dysfunction, reinterventions, procedure duration and overall survival. Study quality will be assessed using the Cochrane Risk of Bias Tool. Meta-analysis will be performed using RevMan V.5.3 statistical software. Data will be combined with a random effect model. The results will be presented as a risk ratio for dichotomous data, weighted mean difference for continuous data and HR for time-to-event data. Publication bias will be visualised using funnel plots.Ethics and disseminationThis study will not use primary data, and therefore, formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences.PROSPERO registration numberCRD42018117040

The results from epidemiological studies between dietary vitamin A intake and glioma risk is not consistent. Thus, a meta-analysis was conducted to confirm the exact relationship between them. PubMed and Web of Knowledge were used to search the relevant articles up to May 2015. Pooled relative risk (RR) with 95% confidence interval (CI)was calculated using random-effect model. Egger’s test was used to assess the small-study effect. At the end, seven articles with eight case-control studies involving 1841 glioma cases and 4123 participants were included. Our study indicated that highest category of dietary vitamin A intake was significantly associated with reduced risk of glioma (RR = 0.80, 95% CI = 0.62–0.98, p = 0.014, I2 = 54.9%). Egger’s test did not find any publication bias. In conclusion, our study indicated that higher category of dietary vitamin A intake could reduce the glioma risk. However, we could not do a dose-response analysis for vitamin A intake with glioma risk due to the limited data in each reported individual article. Due to this limitation, further studies with detailed dose, cases and person-years for each category is wanted to assess this dose-response association.

This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 10 6 human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

In this study, an LC wireless passive humidity sensor based on MoS2 nanoflakes was proposed. The LC wireless passive humidity sensor was optimized by performing HFSS simulations and fabricated via a screen-printing technique. The MoS2 nanoflakes were characterized by laser scanning confocal microcopy, scanning electron microscope, and X-ray diffraction. The measurements show the sensor can operate stably for a long time with a hysteresis of 4% RH (relative humidity) in 10⁻95% RH. At low humidity environment (10⁻60% RH), the sensitivity of the as-prepared humidity sensor is 2.79 kHz/% RH, and a sensitivity of 76.04 kHz/% RH was realized in a high humidity environment (60⁻95% RH). In this regard, the sensing mechanism was discussed in the scope of proton transfer theory. The test results also indicate that the response time and recovery time of the prepared sensor are 10 s, 15 s, respectively and between 15~40 °C the sensitivity of sensor was not temperature-dependent in the range of 10~80% RH. In addition, the sensor shows less sensitivity to temperature in the 15⁻25 °C range at 90% RH. All of these experimental results show that the prepared LC wireless passive humidity sensor can stably monitor the rapidly changing humidity in a sealed and narrow environment for a long time.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. In July 2013, the first human infection with SFTS virus (SFTSV) was detected in Shaanxi Province, Western China. Methods: A seroprevalence study among humans was carried out in an SFTS endemic village; specifically, serum samples were collected from 363 farmers in an SFTS endemic village in Shaanxi Province. The presence of SFTSV antibodies in serum was determined using an ELISA. Results: SFTSV antibodies were found in a total of 20 people (5.51%), with no significant difference between males and females (6.93% and 4.42%, respectively; Chi-square = 1.29, p = 0.25). Moreover, the SFTSV antibody positive rate was not significantly different across different age groups (Chi-square = 2.23, p = 0.69). Conclusions: SFTSV readily infects humans with outdoor exposure. The results of the serological study indicate that the virus circulates widely in Shaanxi Province. SFTSV represents a public health threat in China.

Flexible electronics, which can be distributed on any surface we need, are highly demanded in the development of Internet of Things (IoT), robot technology and electronic skins. Temperature is a fundamental physical parameter, and it is an important indicator in many applications. Therefore, a flexible temperature sensor is required. Here, we report a simple method to fabricate three lightweight, low-cost and flexible temperature sensors, whose sensitive materials are reduced graphene oxide (r-GO), single-walled carbon nanotubes (SWCNTs) and multi-wall carbon nanotubes (MWCNTs). By comparing linearity, sensitive and repeatability, we found that the r-GO temperature sensor had the most balanced performance. Furthermore, the r-GO temperature sensor showed good mechanical properties and it could be bent in different angles with negligible resistance change. In addition, the performance of the r-GO temperature sensor remained stable under different kinds of pressure and was unaffected by surrounding environments, like humidity or other gases, because of the insulating layer on its sensitive layer. The easy-fabricated process and economy, together with the remarkable performance of the r-GO temperature sensor, suggest that it is suitable for use as a robot skin or used in the environment of IoT.

BackgroundMitochondrial DNA polymerase gamma (POLG1) mutations were associated with levodopa-responsive Parkinsonism. POLG1 gene contains a number of common nonsynonymous SNPs and intronic regulatory SNPs which may have functional consequences. It is of great interest to discover polymorphisms variants associated with Parkinson's disease (PD), both in isolation and in combination with specific SNPs.Materials and methodsWe conducted a case-control study and genotyped twenty SNPs and poly-Q polymorphisms of POLG1 gene including in 344 Chinese sporadic PD patients and 154 healthy controls. All the polymorphisms of POLG1 we found in this study were sequenced by PCR products with dye terminator methods using an ABI-3100 sequencer. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) for association between twenty POLG1 SNPs and PD were calculated using the program Haploview.Principal resultsWe provided evidence for strong association of four intronic SNPs of the POLG1 gene (new report: c.2070-12T>A and rs2307439: c.2070-64G>A in intron 11, P = 0.00011, OR = 1.727; rs2302084: c.3105-11T>C and rs2246900: c.3105-36A>G in intron 19, P = 0.00031, OR = 1.648) with PD. However, we did not identify any significant association between ten exonic SNPs of POLG1 and PD. Linkage disequilibrium analysis indicated that c.2070-12T>A and c.2070-64G>A could be parsed into one block as Haplotype 1 as well as c.3105-11T>C and c.3105-36A>G in Haplotype 2. In addition, case and control study on association of POLG1 CAG repeat (poly-Q) alleles with PD showed a significant association (P = 0.03, OR = 2.16) of the non-10/11Q variants with PD. Although intronic SNPs associated with PD didn't influence POLG1 mRNA alternative splicing, there was a strong association of c.2070-12T>A and c.2070-64G>A with decreased POLG1 mRNA level and protein levels.ConclusionsOur findings indicate that POLG1 may play a role in the pathogenesis of PD in Chinese populations.

Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired.Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD(50)) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin.This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity.