Phenotypic Differentiation Is Associated with Gender Plasticity and Its Responsive Delay to Environmental Changes in Alternanthera philoxeroides – Phenotypic Differentiation in Alligator Weed

Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel traits and taxonomic diversity

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

Mesoscopic structure and social aspects of human mobility

The individual movements of large numbers of people are important in many contexts, from urban planning to disease spreading. Datasets that capture human mobility are now available and many interesting features have been discovered, including the ultra-slow spatial growth of individual mobility. However, the detailed substructures and spatiotemporal flows of mobility - the sets and sequences of visited locations - have not been well studied. We show that individual mobility is dominated by small groups of frequently visited, dynamically close locations, forming primary "habitats" capturing typical daily activity, along with subsidiary habitats representing additional travel. These habitats do not correspond to typical contexts such as home or work. The temporal evolution of mobility within habitats, which constitutes most motion, is universal across habitats and exhibits scaling patterns both distinct from all previous observations and unpredicted by current models. The delay to enter subsidiary habitats is a primary factor in the spatiotemporal growth of human travel. Interestingly, habitats correlate with non-mobility dynamics such as communication activity, implying that habitats may influence processes such as information spreading and revealing new connections between human mobility and social networks.Comment: 7 pages, 5 figures (main text); 11 pages, 9 figures, 1 table (supporting information

All-Electrical Skyrmionic Bits in a Chiral Magnetic Tunnel Junction

Topological spin textures such as magnetic skyrmions hold considerable promise as robust, nanometre-scale, mobile bits for sustainable computing. A longstanding roadblock to unleashing their potential is the absence of a device enabling deterministic electrical readout of individual spin textures. Here we present the wafer-scale realization of a nanoscale chiral magnetic tunnel junction (MTJ) hosting a single, ambient skyrmion. Using a suite of electrical and multi-modal imaging techniques, we show that the MTJ nucleates skyrmions of fixed polarity, whose large readout signal - 20-70% relative to uniform states - corresponds directly to skyrmion size. Further, the MTJ exploits complementary mechanisms to stabilize distinctly sized skyrmions at zero field, thereby realizing three nonvolatile electrical states. Crucially, it can write and delete skyrmions using current densities 1,000 times lower than state-of-the-art. These results provide a platform to incorporate readout and manipulation of skyrmionic bits across myriad device architectures, and a springboard to harness chiral spin textures for multi-bit memory and unconventional computing.Comment: 8 pages, 5 figure

Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Opportunities and barriers for providing HIV testing through community health centers in mainland China: a nationwide cross-sectional survey

Abstract: Background: Primary care may be an avenue to increase coverage of HIV testing but it is unclear what challenges primary healthcare professionals in low- and middle-income countries face. We describe the HIV testing practices in community health centres (CHCs) and explore the staff’s attitude towards further development of HIV testing services at the primary care level in China. Methods: We conducted a national, cross-sectional survey using a stratified random sample of CHCs in 20 cities in 2015. Questionnaires were completed by primary care doctors and nurses in CHCs, and included questions regarding their demographics, clinical experience and their views on the facilitators and barriers to offering HIV testing in their CHC. Multivariate logistic regression was conducted to examine the association between staff who would offer HIV testing and their sociodemographic characteristics. Results: A total of 3580 staff from 158 CHCs participated. Despite the majority (81%) agreeing that HIV testing was an important part of healthcare, only 25% would provide HIV testing when requested by a patient. The majority (71%) were concerned about reimbursement, and half (47%) cited lack of training as a major barrier. Almost half (44%) believed that treating people belonging to high-risk populations would scare other patients away, and 6% openly expressed their dislike of people belonging to high-risk populations. Staff who would offer HIV testing were younger (adjusted odds ratio (aOR) 0.97 per year increase in age, 95% confidence interval (CI):0.97–0.98); trained as a doctor compared to a nurse (aOR 1.79, 95%CI:1.46–2.15); held a bachelor degree or above (aOR 1.34, 95%CI:1.11–1.62); and had previous HIV training (aOR 1.55, 95%CI:1.27–1.89). Conclusions: Improving HIV training of CHC staff, including addressing stigmatizing attitudes, and improving financial reimbursement may help increase HIV testing coverage in China

Opportunities and barriers for providing HIV testing through community health centers in mainland China: a nationwide cross-sectional survey

Abstract: Background: Primary care may be an avenue to increase coverage of HIV testing but it is unclear what challenges primary healthcare professionals in low- and middle-income countries face. We describe the HIV testing practices in community health centres (CHCs) and explore the staff’s attitude towards further development of HIV testing services at the primary care level in China. Methods: We conducted a national, cross-sectional survey using a stratified random sample of CHCs in 20 cities in 2015. Questionnaires were completed by primary care doctors and nurses in CHCs, and included questions regarding their demographics, clinical experience and their views on the facilitators and barriers to offering HIV testing in their CHC. Multivariate logistic regression was conducted to examine the association between staff who would offer HIV testing and their sociodemographic characteristics. Results: A total of 3580 staff from 158 CHCs participated. Despite the majority (81%) agreeing that HIV testing was an important part of healthcare, only 25% would provide HIV testing when requested by a patient. The majority (71%) were concerned about reimbursement, and half (47%) cited lack of training as a major barrier. Almost half (44%) believed that treating people belonging to high-risk populations would scare other patients away, and 6% openly expressed their dislike of people belonging to high-risk populations. Staff who would offer HIV testing were younger (adjusted odds ratio (aOR) 0.97 per year increase in age, 95% confidence interval (CI):0.97–0.98); trained as a doctor compared to a nurse (aOR 1.79, 95%CI:1.46–2.15); held a bachelor degree or above (aOR 1.34, 95%CI:1.11–1.62); and had previous HIV training (aOR 1.55, 95%CI:1.27–1.89). Conclusions: Improving HIV training of CHC staff, including addressing stigmatizing attitudes, and improving financial reimbursement may help increase HIV testing coverage in China

First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy. RESULTS: Forty-eight patients were enrolled (dose escalation, n = 40; dose expansion, n = 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, n = 1) and hypertension (15 mg, n = 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; n = 7) or stable disease (SD) ≥ 24 weeks (n = 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR n = 3; SD ≥ 24 weeks n = 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR n = 2; SD ≥ 24 weeks n = 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR n = 1; SD ≥ 24 weeks n = 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib\u27s half-life was 28-34 hours. CONCLUSIONS: Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials

Factors determining the survival of nasopharyngeal carcinoma with lung metastasis alone: does combined modality treatment benefit?

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) with lung metastasis alone has been reported as a relatively favorable prognostic group, and combined modality treatment might be indicated for selected cases. However, the prognostic factors determining survival of this group and the indication of combined therapy have not been thoroughly studied.</p> <p>Methods</p> <p>We retrospectively reviewed 246 patients of NPC with lung metastasis(es) alone presented at diagnosis or as the first failure after primary treatment from 1993 to 2008 in an academic tertiary hospital. Univariate and multivariate survival analyses of post-metastasis survival (PMS) and overall survival (OS) were carried out to determine the prognostic factors.</p> <p>Results</p> <p>The 3-year, 5-year, and 10-year of PMS and OS for the whole cohort were 34.3%, 17.0%, 8.6% and 67.8%, 45.4%, 18.5%, respectively. The median PMS (45.6 months <it>vs</it>. 23.7 months) and OS (73.7 months <it>vs</it>. 46.2 months) of patients treated with combined therapy was significantly longer than that of those treated with chemotherapy alone (<it>P </it>< 0.001). Age, disease-free interval (DFI) and treatment modality were evaluated as independent prognostic factors of OS, while only age and treatment modality retain their independent significance in PMS analysis. In stratified survival analysis, compared to chemotherapy alone, combined therapy could benefit the patients with DFI > 1 year, but not those with DFI ≤ 1 year.</p> <p>Conclusions</p> <p>Age ≤ 45 years, DFI > 1 year, and the combined therapy were good prognostic factors for NPC patients with lung metastasis(es) alone. The combination of local therapy and the basic chemotherapy should be considered for these patients with DFI > 1 year.</p