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Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019–2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm3, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians’ concerns and patients’ refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.

We investigated the neural correlates for chronic cancer pain conditions by retrospectively analyzing whole brain regions on 18F-fluoro-2-deoxyglucose-positron emission tomography images acquired from 80 patients with head and neck squamous cell carcinoma and esophageal cancer. The patients were divided into three groups according to perceived pain severity and type of analgesic treatment, namely patients not under analgesic treatment because of no or minor pain, patients with good pain control under analgesic treatment, and patients with poor pain control despite analgesic treatment. Uncontrollable cancer pain enhanced the activity of the hippocampus, amygdala, inferior temporal gyrus, and temporal pole. Metabolic connectivity analysis further showed that amygdala co-activation with the hippocampus was reduced in the group with poor pain control and preserved in the groups with no or minor pain and good pain control. The increased although imbalanced activity of the medial temporal regions may represent poor pain control in patients with cancer. The number of patients who used anxiolytics was higher in the group with poor pain control, whereas the usage rates were comparable between the other two groups. Therefore, further studies should investigate the relationship between psychological conditions and pain in patients with cancer and analyze the resultant brain activity.Trial registration: This study was registered at clinicaltrials.gov on 9/3/20 (NCT04537845).

Neurons convert the external stimuli into action potentials, or spikes, and encode the contained information into the biological nerve system. Despite the complexity of neurons and the synaptic interactions in between, the rate models are often adapted to describe neural encoding with modest success. However, it is not clear whether the firing rate, the reciprocal of the time interval between spikes, is sufficient to capture the essential feature for the neuronal dynamics. Going beyond the usual relaxation dynamics in Ginzburg-Landau theory for statistical systems, we propose the neural activities can be captured by the U(1) dynamics, integrating the action potential and the ``phase" of the neuron together. The gain function of the Hodgkin-Huxley neuron and the corresponding dynamical phase transitions can be described within the U(1) neuron framework. In addition, the phase dependence of the synaptic interactions is illustrated and the mapping to the Kinouchi-Copelli neuron is established. It suggests that the U(1) neuron is the minimal model for single-neuron activities and serves as the building block of the neuronal network for information processing., Comment: 11 pages, 11 figures

Drug-eluting bead transarterial chemoembolization (DEB-TACE) is the most common treatment for unresectable hepatocellular carcinoma (HCC). However, the effect of drug loading concentration and microsphere size on treatment outcomes remains unclear. This retrospective study compares the outcomes of 87 HCC patients who underwent DEB-TACE with half-loaded or full-loaded doxorubicin (maximum capacity 50 mg/mL) in 75-µm or 100-µm microspheres. Treatment with 100-μm microspheres resulted in significantly lower rates of procedure-related complications (6.6% vs. 26.9%; P

Longhorn beetles are extremely rich wood-boring insects possessing larvae that feed on the xylem of trees and/or lianas, which have detrimental effects on plants; in turn, the hosting plants may play a fundamental role in shaping the longhorn beetle community assemblage. However, factors determining the community assemblage of wood-boring longhorn beetles, particularly along the multiple spatial scales is still in need of further exploration. In this study, we designed an experiment across several spatial scales (from local to macro scales) from tropical to temperate climate gradients in Yunnan province, southwest China to examine to what extend the attributes of host-specificity is shaping the community assemblage along different spatial scales. This study concludes that (1) the wood-boring longhorn beetles showed attributes of host-specificity to a certain degree at the community level, (2) biotic (host plant specificity) and abiotic (climatic gradients) factors jointly shaped community composition of this species along the multiple spatial scales, (3) biotic interactions have a prominent effect on the community composition of this species at local-scale while macroclimatic gradients impose the major control on it at macro-scale. Thus, this study highlights the significance of host specificity in affecting the wood-boring longhorn beetle community assemblage, particularly at local scales.

A single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0–1000 µA). The chest–pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH.Clinical Trial Registration This clinical trial was prospectively registered at www.clinicaltrials.gov with the Unique identifier: NCT03554941. Date of registration: (13/06/2018).

For women with recurrent urinary tract infection (UTI), previous U101 study has shown that pentosan polysulfate sodium (PPS) monotherapy for 16 weeks significantly reduced UTI episodes in the treatment group throughout the trial period. In this follow-up study, we aimed to assess whether the effects of PPS would last after completion of the trial to prevent recurrent UTIs. Conducted from 2018 to 2019, the U101 study was a multicenter, prospective, phase 2a, randomized trial, enrolling women with recurrent UTI to study the effects of a 16-week oral PPS monotherapy. After approximately two years, the follow-up was conducted by phone interview, obtaining data including self-reported UTI events, quality of life questionnaire, and adverse events. The primary endpoint of follow-up study was UTI recurrence-free survival and the secondary endpoints were quality of life and adverse events. Approximately two years after completion of the trial, the rate of recurrent UTI was 25% (3 of the 12 patients) in the PPS group and 85.7% (12 of the 14 patients) in the control group. Over the entire follow-up period, the UTI recurrence-free survival was significantly better in the PPS group than in the control group (log-rank test p p

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). Despite the existing extensive research, the molecular and pathogenic mechanisms of ccRCC are elusive. We aimed to identify the immune-related lncRNA signature and molecular subtypes associated with ccRCC. By integrating 4 microarray datasets from Gene Expression Omnibus database, we identified 49 immune-related genes. The corresponding immune-related lncRNAs were further identified in the TCGA dataset. 12-lncRNAs prognostic and independent signature was identified through survival analysis and survival difference between risk groups was further identified based on the risk score. Besides, we identified 3 molecular subtypes and survival analysis result showed that cluster 2 has a better survival outcome. Further, ssGSEA enrichment analysis for the immune-associated gene sets revealed that cluster 1 corresponded to a high immune infiltration level. While cluster 2 and cluster 3 corresponded to low and medium immune infiltration level, respectively. In addition, we validated the 12-lncRNA prognostic signature and molecular subtypes in an external validation dataset from the ICGC database. In summary, we identified a 12-lncRNA prognostic signature which may provide new insights into the molecular mechanisms of ccRCC and the molecular subtypes provided a theoretical basis for personalized treatment by clinicians.

In non-small-cell lung cancer, mutation of epidermal growth factor receptor (EGFR) stimulates cell proliferation and survival. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are used as first-line therapy with drastic and immediate effectiveness. However, the disease eventually progresses in most cases within a few years due to the development of drug resistance. Here, we explored the role of progesterone membrane component 1 (PGRMC1) in acquired resistance to erlotinib and addressed the molecular mechanism of EGFR-TKI resistance induced by PGRMC1. The erlotinib-sensitive cell line PC9 (derived from non-small-cell lung cancer) and the erlotinib-resistant cell line PC9/ER were used. In proteomic and immunoblotting analyses, the PGRMC1 level was higher in PC9/ER cells than in PC9 cells. WST-8 assay revealed that inhibition of PGRMC1 by siRNA or AG-205, which alters the spectroscopic properties of the PGRMC1-heme complex, in PC9/ER cells increased the sensitivity to erlotinib, and overexpression of PGRMC1 in PC9 cells reduced their susceptibility to erlotinib. In the presence of erlotinib, immunoprecipitation assay showed that AG-205 suppressed the interaction between EGFR and PGRMC1 in PC9/ER cells. AG-205 decreased the expression of β-catenin, accompanied by up-regulation of IκBα (also known as NFKBIA). Furthermore, AG-205 reduced the expression of β-TrCP (also known as BTRC), suggesting that PGRMC1 enhanced the crosstalk between NF-κB (also known as NFKB) signaling and Wnt/β-catenin signaling in an erlotinib-dependent manner. Finally, treatment with the Wnt/β-catenin inhibitor XAV939 enhanced the sensitivity of PC9/ER cells to erlotinib. These results suggest that PGRMC1 conferred resistance to erlotinib through binding with EGFR in PC9/ER cells, initiating crosstalk between the Wnt/β-catenin and NF-κB pathways.

Wind is one of the cleanest renewable energy resources. Through the “Thousand Wind Turbines Project”, Taiwan is planning to increase the proportion of power generation from renewable energy and has set a target of 5.7 GW for offshore wind by 2025. The effects of future offshore wind farms (OWFs) over the Taiwan Strait on the atmospheric environment have not been evaluated. This study examined the potential effects of proposed OWFs on the atmospheric environment if the OWFs had existed during Tropical Storm Haitang (2017) by using Weather Research and Forecasting (WRF) model. A small set of ensemble simulations was conducted for studying the sensitivity of the ambient conditions in the region to the wind farm locations, the number and density of the turbines, and the initial time of simulations. Following the landfall and northward movement of Tropical Storm Haitang, a series of complex interactions between the typhoon circulation and the wind farm emerged, including small time slots of wake effect and mountain blocking effect. The combination of these rapidly changing OWFs-related effects contributed to a weak reduction in precipitation (− 1.08 mm) and hub-height wind speed (− 0.25 m s−1), as well as minimal warming near the surface (+ 0.13 °C) over southern Taiwan.

Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2–2.3 mm at vertical bone height and 2.8–3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.

Pyrite nodules up to 20 cm in diameter are found at the top of the Marinoan (~ 635 Ma) Nantuo glacial diamictite as well as in the cap dolostones and shale/siltstones in the lower Doushantuo Formation in eastern Guizhou, southern China. Field occurrences, petrography, and stable sulfur isotopic compositions of pyrite nodules were studied from a section at Taoying, eastern Guizhou, China. Pyrite δ34S values from different nodules varied from 7.3 to 60.5‰ at different stratigraphic levels. No stratigraphic trend existed for the δ34S, supporting the scenario of pyrite formation in sediments before the precipitation of the cap dolostone. Pyrite δ34S values were also homogeneous within individual nodules at a 0.3 to 1 cm sampling scale, but were more heterogeneous at a 2 mm sampling scale. Homogeneity was not expected from the particular model for pyrite nodule formation in a largely closed or semi-closed environment. Thus, differential cementation and compaction of the pyrite-bearing sediments may have produced the nodular shape of the pyrite deposit.

Given the new spread and potential damage of the fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) in Asia, it has become imperative to understand the development biology of this invasive species on selected vegetable crops in newer geographical regions. In this study, we investigated the ovipositional preference of FAW females on different host plants, under choice- and non-choice tests. In addition, using the age-stage, two-sex life table theory, we assessed the performance of immature FAW individuals fed and reared on selected vegetable crops to get information related to development time, survival, reproduction and longevity. Fall armyworm females had an oviposition preference on maize compared to other vegetable crops, including cabbage and soybean, and reluctance for tomato, which was confirmed during the choice and non-choice tests. In contrast to the oviposition preference, our results also suggest that despite low preference for cabbage, soybean, and tomato, these crops seemed to provide a high benefit for an appropriate offspring performance, exceeding in some cases the benefits from a maize-based diet. Information from this study was discussed in terms of FAW ecology and how female's decision affects their reproductive fitness, and the survival and performance of its offspring.

Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

Levels of amyloid-β (Aβ) and tau peptides in brain have been associated with Alzheimer disease (AD). The current study investigated the abilities of plasma Aβ42 and total-tau (t-tau) levels in predicting cognitive decline in subjects with amnestic mild cognitive impairment (MCI). Plasma Aβ42 and t-tau levels were quantified in 22 participants with amnestic MCI through immunomagnetic reduction (IMR) assay at baseline. The cognitive performance of participants was measured through neuropsychological tests at baseline and annual follow-up (average follow-up period of 1.5 years). The predictive value of plasma Aβ42 and t-tau for cognitive status was evaluated. We found that higher levels of Aβ42 and t-tau are associated with lower episodic verbal memory performance at baseline and cognitive decline over the course of follow-up. While Aβ42 or t-tau alone had moderate-to-high discriminatory value in the identification of future cognitive decline, the product of Aβ42 and t-tau offered greater differential value. These preliminary results might suggest that high levels of plasma Aβ42 and t-tau in amnestic MCI are associated with later cognitive decline. A further replication with a larger sample over a longer time period to validate and determine their long-term predictive value is warranted.

Achieving smoke-free healthcare facilities remains a great challenge in countries with a high smoking prevalence and weak regulation. Assessment of the impact of environmental tobacco smoke (ETS) and its constituent PM2.5 on the air quality in Chinese hospitals has not been reported. In this study, we conducted air quality surveys by measuring real-time PM2.5 concentrations with Dylos Air Quality Monitors in five tertiary hospitals in Shantou, China during summer (July-August 2016) and winter (November-February 2017). Twenty-eight-day surveys inside the hospitals showed median PM2.5 concentrations above the China Air Quality Standard in elevator lobbies (51.0 μg/m3, IQR 34.5–91.7), restrooms (40.2, 27.1–70.3), and corridors (36.5, 23.0–77.4). Evidence of tobacco smoking was significantly associated with PM2.5 spikes observed in all the survey locations, contributing to the air quality undesirable for health in 49.1% of total survey hours or 29.3% of summer and 75.4% of winter survey hours inside the buildings, and 33.5%, 25.7%, and 6.8% of survey hours in doctor offices, nurse stations, and patient rooms, respectively. In conclusion, smoking inside hospitals induces PM2.5 spikes that significantly compromise the air quality and impose significant health risk to the hospital inhabitants. Reinforcing comprehensive smoking ban with the vested interest of all stakeholders followed by creative disciplinary actions are suggested to ensure healthcare safety.

A major number of studies have demonstrated Beta-tricalcium phosphate (β-TCP) biocompatibility, bioactivity, and osteoconductivity characteristics in bone regeneration. The aim of this research was to enhance β-TCP's biocompatibility, and evaluate its physicochemical properties by argon glow discharge plasma (GDP) plasma surface treatment without modifying its surface. Treated β-TCP was analyzed by scanning electron microscopy (SEM), energy-dispersive spectrometry, X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis, and Fourier transform infrared spectroscopy characterization. To evaluate treated β-TCP biocompatibility and osteoblastic differentiation, water-soluble tetrazolium salts-1 (WST-1), immunofluorescence, alkaline phosphatase (ALP) assay, and quantitative real-time polymerase chain reaction (QPCR) were done using human mesenchymal stem cells (hMSCs). The results indicated a slight enhancement of the β-TCP by GDP sputtering, which resulted in a higher Ca/P ratio (2.05) than the control. Furthermore, when compared with control β-TCP, we observed an improvement of WST-1 on all days (p p p

Open spina bifida or myelomeningocele (MMC) is a devastating neurologic congenital defect characterized by primary failure of neural tube closure of the spinal column during the embryologic period. Cerebrospinal fluid leak caused by the MMC spinal defect in the developing fetus can result in a constellation of encephalic anomalies that include hindbrain herniation and hydrocephalus. The exposure of extruded spinal cord to amniotic fluid also poses a significant risk for inducing partial or complete paralysis of the body parts beneath the spinal aperture by progressive spinal cord damage in-utero. A randomized trial demonstrated that prenatal repair by fetal surgery, sometimes using patches, to cover the exposed spinal cord with a watertight barrier is effective in reducing the postnatal neurologic morbidity as evidenced by decreased incidence and severity of postnatal hydrocephalus and the reduced need for ventricular-peritoneal shunting. Currently, the use of inert or collagen-based patches are associated with high costs and inadequate structural properties. Specifically, the inert patches do not degrade after implantation, causing the need for a post-natal removal surgery associated with trauma for the newborn. Our present study is aimed towards in-vitro degradation studies of a newly designed patch, which potentially can serve as a superior alternative to existing patches for MMC repair. This novel patch was fabricated by blending poly(l-lactic acid) and poly(ε-caprolactone). The 16-week degradation study in amniotic fluid was focused on tracking changes in crystallinity and mechanical properties. An additional set of designed patches was exposed to phosphate-buffered saline (PBS), as a time-paired control. Crystallinity studies indicate the progress of hydrolytic degradation of the patch in both media, with a preference to bulk erosion in phosphate buffered saline and surface erosion in amniotic fluid. Mechanical testing results establish that patch integrity is not compromised up to 16 weeks of exposure either to body fluids analog (PBS) or to amniotic fluid.

We sought to compare the vaginal microbiota profiles of Taiwanese women with severe preeclampsia (SPE) and normotensive control pregnancies. In a discovery cohort, vaginal swab samples and paired blood specimens were simultaneously obtained at the time of caesarean delivery from 30 women with SPE and 30 controls. The composition of vaginal microbiota was characterised by 16S ribosomal RNA gene sequencing of the V3–V4 region. Results were subsequently validated by real-time qPCR. We sought confirmation of our findings in an expanded cohort consisting of 58 women with SPE and 55 controls. In both the discovery and confirmation cohorts, women with SPE had higher relative abundance of Prevotella bivia in their vaginal microbial community (P = 0.006 and 0.011, respectively). Plasma levels of tumour necrosis factor alpha (TNF-α) were higher when compared with controls (P = 0.031) in the confirmation cohort. Three variables (vaginal Prevotella bivia, plasma TNF-α, and body mass index [BMI]) were included in a prediction panel for SPE. Of these, BMI was the most predictive variable. The area under the curve (AUC) of predicted probability values for the three-variable panel revealed that it can discriminate between SPE and normotensive pregnancies with good accuracy (AUC = 0.797, P Prevotella bivia in vaginal microbiota, which is tightly regulated by BMI, may be involved in the pathogenesis of SPE.

Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility. Our results show that HAI-2 overexpression suppressed matriptase-induced prostate cancer cell motility. We demonstrate that HAI-2 interacts with matriptase on cell surface and inhibits matriptase proteolytic activity. Moreover, cellular HAI-2 harnesses its Kunitz domain 1 (KD1) to inhibit matriptase activation and prostate cancer cell motility although recombinant KD1 and KD2 of HAI-2 both show an inhibitory activity and interaction with matriptase protease domain. The results together indicate that HAI-2 is a cognate inhibitor of matriptase, and KD1 of HAI-2 plays a major role in the inhibition of cellular matritptase activation as well as human prostate cancer invasion.

The one month survival rate after out-of-hospital cardiac arrest (OHCA) in the paediatric population remains low. Improving survival in paediatric OHCA by enhancing the quality of cardiopulmonary resuscitation (CPR) is important. In this study, we aimed to analyse the factors associated with CPR quality by using a real-time feedback device. Participants were prospectively divided into 4 groups: paediatric research fellows, paediatric residents, medical students (clerks), and paediatric critical care nurses. Then, the participants were asked to perform 5 cycles of CPR on a paediatric simulation manikin without prompts from feedback devices, and to repeat another 5 cycles of CPR after education with the 2015 paediatric advanced life support guidelines. A total of 75 participants were evaluated. In the overall analysis, an improvement in the percentage of participants meeting the target compression rate was observed (from 49.82% to 71.23%, P P = 0.005). Among the 4 groups, the residents showed the most significant improvement in both compression rate (from 48.41% to 86.57%, P P , the real-time CPR feedback device may help clinical physicians and nurses in improving the quality of chest compression. Excessive CPR compression rate may be a major cause of inadequate CPR performance.

Inertial particle focusing in curved channels has enormous potential for lab-on-a-chip applications. This paper compares a zigzag channel, which has not been used previously for inertial focusing studies, with a serpentine channel and a square wave channel to explore their differences in terms of focusing performance and separation possibilities. The particle trajectories and fluid fields in the curved channels are studied by a numerical simulation. The effects of different conditions (structure, Reynolds number, and particle size) on the competition between forces and the focusing performance are studied. The results indicate that the zigzag channel has the best focusing effect at a high Reynolds number and that the serpentine channel is second in terms of performance. Regarding the particle separation potential, the zigzag channel has a good performance in separating 5 μm and 10 μm particles at ReC = 62.5. In addition, the pressure drop of the channel is also considered to evaluate the channel performance, which has not been taken into account in the literature on inertial microfluidics. This result is expected to be instructive for the selection and optimization of inertial microchannel structures.

There is limited clinical evidence to support the combination of daptomycin and beta-lactam antibiotics (DAP + BLA) for treatment of vancomycin-resistant enterococci (VRE) bloodstream infections (BSI). We conducted a prospective observational cohort study of VRE-BSI during 2010–2015. The primary endpoint was mortality at the end of treatment. We included 114 patients who received DAP for VRE-BSI. Of these 87 (76.3%) received DAP + BLA. There were no significant differences in mortality between the DAP and DAP + BLA groups on univariable analysis (10/27 vs. 34/87, P = 0.85). A subgroup analysis of patients with enterococcal DAP minimum inhibitory concentrations (MICs) ≤2 mg/L, revealed that those treated with DAP + BLA had a lower mortality (adjusted hazard ratio [aHR], 0.23; 95% confidence interval [CI], 0.06–0.93; P = 0.04) after adjustment for other significant predictors of mortality, including the DAP dose. In addition, patients receiving high-dose (≥9 mg/kg) DAP + BLA independently had a better survival than those receiving low-dose DAP alone (aHR = 5.16), low-dose DAP + BLA (aHR = 5.39), and high-dose DAP alone (aHR = 19.01) (P

We have prepared and tested a new surface enhanced Raman scattering (SERS) substrate based on self-assembled graphitic sheets to detect bisphenol A (BPA) in plastic consumer goods. Transmission electron microscopy (TEM) and atomic-force microscopy (AFM) were used to characterize the structure of the graphitic sheets and showed a lattice spacing of 0.24 nm and layer height of 0.34 nm. These values were comparable to single monolayer graphene. The effective SERS detection limit of this method is 1 μM BPA, which is lower than the European Union specific migration limit for BPA of 0.6 mg/kg (2.6 μM). When used in salt solutions, graphitic sheets exhibited ultra-sensitivity toward BPA of 0.025 M to 2 M, which was broader than physiological ionic strength (0.14 M) and urinary NaCl (0.17 M). Our results demonstrated that this graphitic sheet based SERS detection platform can be used to determine BPA levels leached from commercial polycarbonate plastic products and for on-site rapid analysis with good results.

Pichia pastoris is a widely used heterologous protein production workhorse. However, with its multiple genetic modifications to solve bottlenecks for heterologous protein productivity, P. pastoris lacks selectable markers. Existing selectable marker recycling plasmids have drawbacks (e.g., slow growth and conditional lethality). Here, zeocin-resistance marker recycling vectors were constructed using the Cre/loxP recombination system. The vectors were used to (i) knock in heterologous phytase, xylanase and lipase expression cassettes, (ii) increase the phytase, xylanase and lipase gene copy number to 13, 5, and 5, respectively, with vector introduction and (iii) engineer the secretion pathway by co-overexpressing secretion helper factors (Sly1p and Sec1p) without introducing selectable markers, giving a phytase field of 0.833 g/L. The vectors allow selectable marker recycling and would be a useful tool to engineer P. pastoris for high heterologous protein productivity.

A series of (1-x)Bi0.48La0.02Na0.48Li0.02Ti0.98Zr0.02O3-xNa0.73Bi0.09NbO3 ((1-x)LLBNTZ-xNBN) (x = 0-0.14) ceramics were designed and fabricated using the conventional solid-state sintering method. The phase structure, microstructure, dielectric, ferroelectric and energy storage properties of the ceramics were systematically investigated. The results indicate that the addition of Na0.73Bi0.09NbO3 (NBN) could decrease the remnant polarization (P r ) and improve the temperature stability of dielectric constant obviously. The working temperature range satisfying TCC150 °C ≤±15% of this work spans over 400 °C with the compositions of x ≥ 0.06. The maximum energy storage density can be obtained for the sample with x = 0.10 at room temperature, with an energy storage density of 2.04 J/cm3 at 178 kV/cm. In addition, the (1-x)LLBNTZ-xNBN ceramics exhibit excellent energy storage properties over a wide temperature range from room temperature to 90 °C. The values of energy storage density and energy storage efficiency is 0.91 J/cm3 and 79.51%, respectively, for the 0.90LLBNTZ-0.10NBN ceramic at the condition of 100 kV/cm and 90 °C. It can be concluded that the (1-x)LLBNTZ-xNBN ceramics are promising lead-free candidate materials for energy storage devices over a broad temperature range.

Gene manipulation is essential for metabolic engineering and synthetic biology, but the current general gene manipulation methods are not applicable to the non-model strain Corynebacterium glutamicum (C. glutamicum) ATCC14067, which is used for amino acid production. Here, we report an effective and sequential deletion method for C. glutamicum ATCC14067 using the exonuclease-recombinase pair RecE + RecT (RecET) for recombineering via a designed self-excisable linear double-strand DNA (dsDNA) cassette, which contains the Cre/loxP system, to accomplish markerless deletion. To the best of our knowledge, this is the first effective and simple strategy for recombination with markerless deletion in C. glutamicum ATCC14067. This strategy provides a simple markerless deletion strategy for C. glutamicum and builds a solid basis for producer construction.

Traumatic brain injury (TBI) is the leading cause of pediatric morbidity and mortality worldwide, and half of all fatalities occur in infants aged less than 1 year. We analyzed 129 infants diagnosed with TBI complicated with intracranial hemorrhage confirmed by brain computed tomography. We defined delta hemoglobin (ΔHB) as nadir HB - age specific mean HB, and the ratio of HB (%) as ΔHB/age specific mean HB x 100. Infants with poor neurologic outcomes had a lower admission HB and ΔHB (p +), 8.24; negative likelihood ratio (LR−), 0.34); the AUC was 0.88 in infants aged from 6–12 months and the optimal cutoff was −20.6% (sensitivity, 89%; specificity, 79%; LR+, 4.13; LR−, 0.15).

Fine particulate matter 2.5 (PM2.5) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM2.5-induced inflammatory responses in mother rats, and PM2.5-induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM2.5-induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM2.5-induced modulation.

Entangled photon pair generation is a crucial task for development of quantum information based technologies, and production of entangled pairs by biexciton cascade decays in semiconductor quantum dots is so far one of the most advanced techniques to achieve it. However, its scalability toward massive implementation requires further understanding and better tuning mechanisms to suppress the fine structure splitting between polarized exciton states, which persists as a major obstacle for entanglement generation from most quantum dot samples. In this work, the influence of electrostatic environment arising from electrically biased electrodes and/or charged impurities on the fine structure splitting of GaAs/AlGaAs droplet epitaxial quantum dots is studied, by means of numerical simulations considering a realistic quantum dot confining potential and electron-hole exchange interaction within a multiband k · p framework. We find that reduction of the fine structure splitting can be substantially optimized by tilting the field and seeding impurities along the droplet elongation axis. Furthermore, our results provide evidence of how the presence of charged impurities and in-plane bias components, may account for different degrees of splitting manipulation in dots with similar shape, size and growth conditions.

The phase and local environment, neighbouring atoms and coordination numbers (CN), for an Al-Cu-Fe multilayer were studied during heating (to 800 °C) and cooling (to room temperature) processes using in-situ X-Ray diffraction (XRD) and in-situ X-ray absorption spectroscopy (XAS) techniques to investigate the formation of Al-Cu-Fe quasicrystals (QCs). In-situ XRD clarified the transition of the ω-Al7Cu2Fe phase to a liquid state at the high temperature which transformed into the QC phase during cooling. The in-situ XAS showed a relatively small shift in distance between Cu-Al and Fe-Al during the phase evolution from RT to 700 °C. The distance between Cu-Cu, however, showed a significant increase from ω-phase at 700 °C to the liquid state at 800 °C, and this distance was maintained after QC formation. Furthermore, the CN of Fe-Al was changed to N = 9 during cooling. Through our observations of changes in CN, atomic distances and the atomic environment, we propose the local structural ordering of the quasicrystalline phase originated from a liquid state via ω-phase. In this study, we give a clear picture of the atomic environment from the crystalline to the quasicrystalline phase during the phase transitions, which provides a better understanding of the synthesis of functional QC nanomaterials.

Ecdysteroid UDP glucosyltransferase (EGT) is a baculovirus-encoded protein which can hinder the normal molting of insects by inactivating 20-hydroxyecdysone (20E). Here we expressed EGT in the last-instar silkworm larvae using the GAL4/ UAS system. Compared with the control, for the EGT overexpressed silkworm, the hemolymph 20E content was significantly decreased, the feeding and spinning periods of the last-instar silkworm larvae were extended, the cocoon shell ratio was significantly increased, and the transformation from silkworm larvae to pupa was blocked. Increasing EGT expression resulted in the decrease of 20E content in the hemolymph of silkworm larvae, treating the EGT overexpressed male silkworm with 20E decreased the larval weight and cocoon shell ratio, confirming that the increase in the availability of nutrients to the cocoon and an increase in the cocoon shell weight in the hybrid transgenic silkworms is because of the EGT-induced reduction in active 20E content. Furthermore, though the sericin and flavonoid contents were increased in the cocoon of the EGT overexpressing silkworm, the production of silk fibroin didn’t change.

In this work, an economical and easy-to-use microcapsule array fabricated by ice printing technique has been realized for ultrasensitive fluorescence quantification of copper ions employing functional nucleic acid strategy. With ice printing, the detection reagents are sealed by polystyrene (PS) film isolation and photopolymer, which guarantees a stable and contamination-free environment for functional nucleic acid reaction. Our microcapsule arrays have shown long-term stability (20 days) under −20 °C storage in frozen form before use. During the Cu2+ on-site detection, 1 μL sample is simply injected into the thawy microcapsule by a microliter syringe under room temperature, and after 20 minutes the fluorescence result can be obtained by an LED transilluminator. This method can realize the detection limit to 100 nM (100 fmol/μL) with high specificity.

Synchrotron radiation core-level photoemission spectroscopy, scanning tunneling microscopy (STM), and first-principles calculations have been utilized to explore the growth processes and the atomic structure of the resulting films during the two-step molecular beam epitaxy (MBE) of In and Bi on the Si(111) surface. Deposition of 1.0-ML Bi on the In/Si(111)-(4 × 1) surface at room temperature results in Bi-terminated BiIn-(4 × 3) structures, which are stable up to ~300 °C annealing. By contrast, deposition of In on the β-Bi/Si(111)-(√3 × √3) surface at room temperature results in three dimensional (3D) In islands. In both cases, annealing at 460 °C results in the same In-terminated In0.75Bi/Si(111)-(2 × 2) surface. Our DFT calculations confirm that the surface energy of In-terminated In0.75Bi/Si(111)-(2 × 2) system is lower than that of Bi-terminated Bi0.75In/Si(111)-(2 × 2). These findings provide means for the control of the polarity of the MBE In-Bi atomically thick films.

Fine particulate matter 2.5 (PM2.5) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM2.5-induced inflammatory responses in mother rats, and PM2.5-induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM2.5-induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM2.5-induced modulation.

Coxsackievirus (CV)-B5 is a common human enterovirus reported worldwide; swine vesicular disease virus (SVDV) is a porcine variant of CV-B5. To clarify the transmission dynamics and molecular basis of host switching between CV-B5 and SVDV, we analysed and compared the VP1 and partial 3Dpol gene regions of these two viruses. Spatiotemporal dynamics of viral transmission were estimated using a Bayesian statistical inference framework. The detected selection events were used to analyse the key molecules associated with host switching. Analyses of VP1 sequences revealed six CV-B5 genotypes (A1–A4 and B1–B2) and three SVDV genotypes (I–III). Analyses of partial 3Dpol revealed five clusters (A–E). The genotypes evolved sequentially over different periods, albeit with some overlap. The major hub of CV-B5 transmission was in China whereas the major hubs of SVDV transmission were in Italy. Network analysis based on deduced amino acid sequences showed a diverse extension of the VP1 structural protein, whereas most sequences were clustered into two haplotypes in the partial 3Dpol region. Residue 178 of VP1 showed four epistatic interactions with residues known to play essential roles in viral host tropism, cell entry, and viral decoating.

Depression is a common mental illness with complex and heterogeneous progression dynamics. Risk grouping of depression treatment population based on their longitudinal patterns has the potential to enable cost-effective monitoring policy design. This paper establishes a rule-based method to identify a set of risk predictive patterns from person-level longitudinal disease measurements by integrating the data transformation, rule discovery and rule evaluation. We further extend the identified rules to create rule-based monitoring strategies to adaptively monitor individuals with different disease severities. We applied the rule-based method on an electronic health record (EHR) dataset of depression treatment population containing person-level longitudinal Patient Health Questionnaire (PHQ)-9 scores for assessing depression severity. 12 risk predictive rules are identified, and the rule-based prognostic model based on identified rules enables more accurate prediction of disease severity than other prognostic models including RuleFit, logistic regression and Support Vector Machine. Two rule-based monitoring strategies outperform the latest PHQ-9 based monitoring strategy by providing higher sensitivity and specificity. The rule-based method can lead to a better understanding of disease dynamics, achieving more accurate prognostics of disease progressions, personalizing follow-up intervals, and designing cost-effective monitoring of patients in clinical practice.

Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility. Our results show that HAI-2 overexpression suppressed matriptase-induced prostate cancer cell motility. We demonstrate that HAI-2 interacts with matriptase on cell surface and inhibits matriptase proteolytic activity. Moreover, cellular HAI-2 harnesses its Kunitz domain 1 (KD1) to inhibit matriptase activation and prostate cancer cell motility although recombinant KD1 and KD2 of HAI-2 both show an inhibitory activity and interaction with matriptase protease domain. The results together indicate that HAI-2 is a cognate inhibitor of matriptase, and KD1 of HAI-2 plays a major role in the inhibition of cellular matritptase activation as well as human prostate cancer invasion.

Currently, there are no recommended alternative assays for HER2 cases deemed equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and specificity of 82.8% and 97.3% respectively, with a kappa value of 0.833 (p 2 = 0.91; Concordance rate = 97%; κ = 0.923, P

A novel two-step approach consisting of hydrothermal process and subsequently selective etching has been developed to prepare flower-like three-dimensional porous Bi2Fe4O9 spheres with good uniformity and highly photocatalytic performance. XRD patterns and SEM images reveal that the Bi2Fe4O9 phase does not exhibit any changes after the etching process, and the crystal morphology evolves from micro-platelets to flower-like three-dimensional porous Bi2Fe4O9 spheres by controlling the experiment parameters. The change of morphology will lead to the significant increase of specific surface area, which would be beneficial to the enhancement of photocatalytic performance owing to prominent absorption in the ultraviolet and visible light region. As compared to Bi2Fe4O9 microplatelets, flower-like three-dimensional porous Bi2Fe4O9 spheres exhibit excellent photocatalytic degration rate of methyl orange (MO).