Wearable-Sensor-Based Weakly Supervised Parkinson's Disease Assessment with Data Augmentation.

Parkinson's disease (PD) is the second most prevalent dementia in the world. Wearable technology has been useful in the computer-aided diagnosis and long-term monitoring of PD in recent years. The fundamental issue remains how to assess the severity of PD using wearable devices in an efficient and accurate manner. However, in the real-world free-living environment, there are two difficult issues, poor annotation and class imbalance, both of which could potentially impede the automatic assessment of PD. To address these challenges, we propose a novel framework for assessing the severity of PD patient's in a free-living environment. Specifically, we use clustering methods to learn latent categories from the same activities, while latent Dirichlet allocation (LDA) topic models are utilized to capture latent features from multiple activities. Then, to mitigate the impact of data imbalance, we augment bag-level data while retaining key instance prototypes. To comprehensively demonstrate the efficacy of our proposed framework, we collected a dataset containing wearable-sensor signals from 83 individuals in real-life free-living conditions. The experimental results show that our framework achieves an astounding 73.48% accuracy in the fine-grained (normal, mild, moderate, severe) classification of PD severity based on hand movements. Overall, this study contributes to more accurate PD self-diagnosis in the wild, allowing doctors to provide remote drug intervention guidance.

Experimental Realization of Geometry-Dependent Skin Effect in a Reciprocal Two-Dimensional Lattice.

Recent studies of non-Hermitian periodic lattices unveiled the non-Hermitian skin effect (NHSE), in which the bulk modes under the periodic boundary conditions (PBC) become skin modes under open boundary conditions. The NHSE is a topological effect owing to the nontrivial spectral winding, and such spectral behaviors appear naturally in nonreciprocal systems. Hence prevailing approaches rely on nonreciprocity to achieve the NHSE. Here, we report the experimental realization of the geometry-dependent skin effect in a two-dimensional reciprocal system, in which the skin effect occurs only at boundaries whose macroscopic symmetry mismatches with the lattice symmetry. The role of spectral reciprocity and symmetry is revealed by connecting reflective channels at given boundaries with the spectral topology of the PBC spectrum. Our work highlights the vital role of reciprocity, symmetry, and macroscopic geometry on the NHSE in dimensionality larger than one and opens new routes for wave structuring using non-Hermitian effects.

Experimental Realization of Stable Exceptional Chains Protected by Non-Hermitian Latent Symmetries Unique to Mechanical Systems.

Lines of exceptional points are robust in the three-dimensional non-Hermitian parameter space without requiring any symmetry. However, when more elaborate exceptional structures are considered, the role of symmetry becomes critical. One such case is the exceptional chain (EC), which is formed by the intersection or osculation of multiple exceptional lines (ELs). In this Letter, we investigate a non-Hermitian classical mechanical system and reveal that a symmetry intrinsic to second-order dynamical equations, in combination with the source-free principle of ELs, guarantees the emergence of ECs. This symmetry can be understood as a non-Hermitian generalized latent symmetry, which is absent in prevailing formalisms rooted in first-order Schrödinger-like equations and has largely been overlooked so far. We experimentally confirm and characterize the ECs using an active mechanical oscillator system. Moreover, by measuring eigenvalue braiding around the ELs meeting at a chain point, we demonstrate the source-free principle of directed ELs that underlies the mechanism for EC formation. Our Letter not only enriches the diversity of non-Hermitian exceptional point configurations, but also highlights the new potential for non-Hermitian physics in second-order dynamical systems.

Fast 3D gravity and magnetic modelling using midpoint quadrature and 2D FFT.

To avoid the problem of the traditional methods consuming large computational resources to calculate the kernel matrix and 2D discrete convolution, we present a novel approach for 3D gravity and magnetic modelling. This method combines the midpoint quadrature method with a 2D fast Fourier transform (FFT) to calculate the gravity and magnetic anomalies with arbitrary density or magnetic susceptibility distribution. In this scheme, we apply the midpoint quadrature method to calculate the volume element of the integral. Then, the convolution of the weight coefficient matrix with density or magnetization is efficiently computed via the 2D FFT. Finally, the accuracy and efficiency of the proposed algorithm are validated by using an artificial model and a real topography model. The numerical results demonstrate that the proposed algorithm's computation time and the memory requirement are decreased by approximately two orders of magnitude compared with the space-wavenumber domain method.

East Gobi megalake systems reveal East Asian Monsoon dynamics over the last interglacial-glacial cycle.

Intense debate persists about the timing and magnitude of the wet phases in the East Asia deserts since the late Pleistocene. Here we show reconstructions of the paleohydrology of the East Gobi Desert since the last interglacial using satellite images and digital elevation models (DEM) combined with detailed section analyses. Paleolakes with a total area of 15,500 km2 during Marine Isotope Stage 5 (MIS 5) were identified. This expanded lake system was likely coupled to an 800-1000 km northward expansion of the humid region in East China, associated with much warmer winters. Humid climate across the Gobi Desert during MIS 5 likely resulted in a dustier MIS 4 over East Asia and the North Pacific. A second wet period characterized by an expanded, albeit smaller, lake area is dated to the mid-Holocene. Our results suggest that the East Asian Summer Monsoon (EASM) might have been much weaker during MIS 3.

Non-Hermitian morphing of topological modes.

Topological modes (TMs) are usually localized at defects or boundaries of a much larger topological lattice1,2. Recent studies of non-Hermitian band theories unveiled the non-Hermitian skin effect (NHSE), by which the bulk states collapse to the boundary as skin modes3-6. Here we explore the NHSE to reshape the wavefunctions of TMs by delocalizing them from the boundary. At a critical non-Hermitian parameter, the in-gap TMs even become completely extended in the entire bulk lattice, forming an 'extended mode outside of a continuum'. These extended modes are still protected by bulk-band topology, making them robust against local disorders. The morphing of TM wavefunction is experimentally realized in active mechanical lattices in both one-dimensional and two-dimensional topological lattices, as well as in a higher-order topological lattice. Furthermore, by the judicious engineering of the non-Hermiticity distribution, the TMs can deform into a diversity of shapes. Our findings not only broaden and deepen the current understanding of the TMs and the NHSE but also open new grounds for topological applications.

[Association of MTHFR gene C677T polymorphism with problem behavior and inheritance pattern among children with autism].

OBJECTIVE: To assess the association of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene with autistic behavior and inheritance pattern of children patients. METHODS: Ninety three autism patients were selected as the study group, whilst 93 healthy children were selected as the control group. The C677T genotype of the MTHFR gene was determined, and the correlation between the genotype and the autistic behavior and inheritance pattern were investigated. RESULTS: MTHFR gene C677T locus revealed three genotypes CC, CT and TT. Compared with the control group, the study group had fewer CC genotype but more TT genotype (P<0.05). Individuals with the three genotypes showed a statistically significant difference in the frequencies of four problem behaviors (P<0.05). Regression analysis showed that at least one T allele encoding the degree of 1 and 2 for the 4 problem behaviors that were statistically different. MTHFR gene C677T genotype was associated with autism under the recessive inheritance model and allelic inheritance model (P<0.05). CONCLUSION: The C677T polymorphism of the MTHFR gene is associated with autistic behaviors. Children with the TT genotype or T allele are at higher risk of developing autism, particularly direct gaze, complex limb movements, self-injurious behavior and hyperactivity 1 and 2 related with the degree of coding.

Complete genome sequence of peony leafroll-associated virus, a novel ampelovirus in subgroup I.

The complete genome sequence of peony leafroll-associated virus (PLRaV) was determined by deep sequencing of ribosomal-RNA-depleted total RNA extracted from a peony plant exhibiting leafroll symptoms. Further PCR and RACE analysis showed that the PLRaV genome consists of 15,406 nucleotides and contains 10 putative open reading frames, with an organization typical of members of the genus Ampelovirus, family Closteroviridae. Amino acid sequence comparisons showed that the viral heat shock protein 70 homolog (HSP70h) shared the highest sequence identity (41.7%) with the corresponding region of grapevine leafroll-associated virus 1, and the coat protein (CP) and RNA-dependent RNA polymerase (RdRp) shared the highest sequence identity (32.1% and 52.3%, respectively) with grapevine leafroll-associated virus 13. Phylogenetic analysis of the HSP70h, CP, and RdRp aa sequences showed that PLRaV clustered with members of subgroup I of the genus Ampelovirus.

Research Progress of Exosome-Loaded miRNA in Osteosarcoma.

Currently, although the improvement of surgical techniques and the development of chemotherapy drugs have brought a certain degree of development to the treatment of osteosarcoma, the treatment of osteosarcoma has many shortcomings, and its treatment is limited. MiRNAs and exosomes can be used as diagnostic tools, and they play an important role in the occurrence and chemotherapy resistance of osteosarcoma. Therefore, providing a new method for the treatment of osteosarcoma is the key to solving this problem. To systematically summarize the research status of exoskeleton drug-loaded miRNA in osteosarcoma, we identified and evaluated 208 studies and found that exosome-carrying miRNA can be used as an index for the diagnosis and prognosis of osteosarcoma and share a certain relationship with chemosensitivity. In addition, exosomes can also be used as a carrier of genetic drugs able to regulate the progression of osteosarcoma. Based on the above findings, we propose suggestions for the future development of this field, aiming to bring new ideas for the early diagnosis and treatment of osteosarcoma.

Identification of a novel alphaendornavirus from Lonicera maackii.

A new alphaendornavirus, tentatively named "Lonicera maackii alphaendornavirus" (LmEV), was identified in a Lonicera maackii plant in Beijing, China, with leaf abnormality of interveinal chlorosis, and its complete genome sequence was determined using small-RNA deep sequencing. The RNA genome of LmEV is 16,176 nt in length and contains a large open reading frame encoding a polyprotein of 5363 aa with conserved domains including a cysteine-rich region, a viral helicase, and an RNA-dependent RNA polymerase. Sequence comparisons showed that LmEV shared the highest nt and aa sequence identity with Vicia faba alphaendornavirus (VfEV) of the genus Alphaendornavirus. In phylogenetic analysis of the RdRp aa sequence LmEV clustered with members of the genus Alphaendornavirus, closest to VfEV. To our knowledge, this is the first report of a novel alphaendornavirus identified in Lonicera maackii. Its effect on the host plant, if any, remains to be investigated.

Extended State in a Localized Continuum.

Bound state in a continuum (BIC) is a spatially confined resonance with its energy embedded in a continuous spectrum of propagative modes, yet their coupling is prohibited. In this Letter, we report the discovery of a generic non-Hermitian phenomenon that we call an "extended state in a localized continuum" (ELC). As the name suggests, the ELC is the inversion of the BIC-a single extended state embedded in a continuous spectrum entirely consisting of localized modes, and its emergence rests in the interplay between the BIC and the non-Hermitian skin effect (NHSE). Herein, the BIC is a zero-energy corner mode that spectrally overlaps with a bulk band in a Hermitian kagome lattice. The ELC emerges with the introduction of the NHSE in a particular way, such that it turns all the bulk states into corner skin modes and simultaneously delocalizes the corner mode. We experimentally realize the ELC using an active mechanical lattice. Our findings not only demonstrate the rich potential of the NHSE but may also spark new wave-based applications.

Evaluation of antimicrobial peptide LL-37 for treatment of Staphylococcus aureus biofilm on titanium plate.

ABSTRACT: The antimicrobial peptide LL-37 belongs to the cathelicidin family and is one of the few human bactericidal peptides with potent antistaphylococcal activity. Staphylococcus aureus is one of the main infection bacteria in orthopedic implant therapy. Biofilm formation after bacterial infection brings more and more severe test for clinical antiinfection treatment.However, there are few studies on LL-37 in S. aureus infection of prosthesis. In this work, addition to research the antibacterial activity and the inhibitory effect on bacterial adhesion of LL-37, an in vitro model of S. aureus biofilm formation on titanium alloy surface was established to observe the inhibitory effect of LL-37.The results showed that LL-37 has a strong antibacterial effect on S. aureus in vitro, and the minimum inhibitory concentration (MIC) is about 0.62 µΜ. Moreover, LL-37 has significant impact on the adhesion of S. aureus when the concentration ≥0.16 µM and significant anti-staphylococcal biofilm effects on static biofilm models at the concentration of 0.31 to 10 µM. Additionally, LL-37 at 5 µM had a significant destructive effect on S. aureus biofilm (P < .05) that formed on the titanium alloy surface.This study further confirmed the role of LL-37 in the process of S. aureus infection, including antimicrobial activities, inhibition of bacterial adhesion, and inhibition of mature biofilm. LL-37 can significantly destroy the stable biofilm structure on the titanium alloy surface in vitro, which may provide a new way for refractory infection caused by S. aureus in titanium alloy prosthesis infection.

Spin-orbit interactions of transverse sound.

Spin-orbit interactions (SOIs) endow light with intriguing properties and applications such as photonic spin-Hall effects and spin-dependent vortex generations. However, it is counterintuitive that SOIs can exist for sound, which is a longitudinal wave that carries no intrinsic spin. Here, we theoretically and experimentally demonstrate that airborne sound can possess artificial transversality in an acoustic micropolar metamaterial and thus carry both spin and orbital angular momentum. This enables the realization of acoustic SOIs with rich phenomena beyond those in conventional acoustic systems. We demonstrate that acoustic activity of the metamaterial can induce coupling between the spin and linear crystal momentum k, which leads to negative refraction of the transverse sound. In addition, we show that the scattering of the transverse sound by a dipole particle can generate spin-dependent acoustic vortices via the geometric phase effect. The acoustic SOIs can provide new perspectives and functionalities for sound manipulations beyond the conventional scalar degree of freedom and may open an avenue to the development of spin-orbit acoustics.

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database.

OBJECTIVE: To investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites. METHODS: HNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010-2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data. RESULTS: A total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination. CONCLUSION: HPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.

Metagenomic Analysis of Marigold: Mixed Infection Including Two New Viruses.

Marigold plants with symptoms of mosaic, crinkle, leaf curl and necrosis were observed and small RNA and ribo-depleted total RNA deep sequencing were conducted to identify the associated viruses. Broad bean wilt virus 2, cucumber mosaic virus, turnip mosaic virus, a new potyvirus tentatively named marigold mosaic virus (MMV) and a new partitivirus named as marigold cryptic virus (MCV) were finally identified. Complete genome sequence analysis showed MMV was 9811 nt in length, encoding a large polyprotein with highest aa sequence identity (57%) with the putative potyvirus polygonatumkingianum virus 1. Phylogenetic analysis with the definite potyviruses based on the polyprotein sequence showed MMV clustered closest to plum pox virus. The complete genome of MCV comprised of dsRNA1 (1583 bp) and dsRNA2 (1459 bp), encoding the RNA-dependent RNA polymerase (RdRp), and coat protein (CP), respectively. MCV RdRp shared the highest (75.7%) aa sequence identity with the unclassified partitivirus ambrosia cryptic virus 2, and 59.0%, 57.1%, 56.1%, 54.5% and 33.7% with the corresponding region of the definite delta-partitiviruses, pepper cryptic virus 2, beet cryptic virus 3, beet cryptic virus 2, pepper cryptic virus 1 and fig cryptic virus, respectively. Phylogenetic analysis based on the RdRp aa sequence showed MCV clustered into the delta-partitivirus group. These findings enriched our knowledge of viruses infecting marigold, but the association of the observed symptom and the identified viruses and the biological characterization of the new viruses should be further investigated.

First Report of broad bean wilt virus-2 in marigold (Tagetes erecta L.) in China.

Broad bean wilt virus 2 (BBWV-2), a member of the genus Fabavirus in the family Secoviridae mainly transmitted by aphids, has been recognized as a severe pathogen affecting the production of horticultural and ornamental plants worldwide (Xia et al. 2020). The virus was reported to infect many plant species mostly belonging to the family Fabaceae in China (Wang et al. 2017). In August 2018, marigold plants with the symptom of mosaic were observed in the field of Huairou, Beijing (Figure S1). Total RNA was extracted from symptomatic leaf samples from a single plant with TRIzol reagent (Invitrogen, Carlsbad, CA) with a standard procedure following the manufacturer's instructions, and small RNAs were isolated for deep sequencing library construction with Illumina TruSeq Small RNA Sample Prep Kit (Illumina, San Diego, CA, USA). The high-throughput sequencing was carried out on an Illumina HiSeq2500 platform. After raw data process, 8,911,917 clean reads were gained and further de novo assembled into contigs with CLC Genomics Workbench software. BLASTN and BLASTX analysis against the GenBank database showed that 81 of the 9,495 assembled contigs shared high nucleotide (nt) sequence identity with the bipartite genome of BBWV-2 isolate Gyp (KX686589-KX686590 for RNA1 and RNA2, 89% of the genome coverage and 90% nt identity) and 34 with high nt sequence identity of cucumber mosaic virus(CMV) from Tagetes erecta (EU665000-EU665002 for RNA1-RNA3,89% of the genome coverage and 96% nt sequence identity) with sequence coverage ranging from 24-fold to 8,078-fold at different genome positions. To further confirm the presence of BBWV-2, a RNA2 specific primer pair targeting the coat protein region (F1423-1448,5-CTGACAGAGGAATACTATTTCCAAAG-3;R2692-2719,5-CCTGTAAAATTGATATCTCCGGACAAAC-3) was designed from the obtained HTS sequence and reverse transcription-polymerase chain reaction (RT-PCR) was conducted. The 1.3 kb amplicon was ligated to pMD19-T vector (TaKaRa, Dalian, China) and sequenced. Sequence analysis showed it (BBWV-2-marigold, MW322809) shared 99% nt sequence identity with the Gyp isolate infecting Gynura procumbens from South Korea (LC497425.1). Phylogenetic analysis constructed with MEGA6 with the CP nt sequence of other reported BBWV-2 isolates showed BBWV-2-marigold clustered closely with the isolates from South Korea infecting Gynura procumbens (Figure S2), in accordance with the sequence identity analysis. Further RT-PCR with primer pair targeting the RNA1 (F3025-3050 5-GACAGAGTGATATTCCTAATCGAGAT-3; R4035-4062CACTCAATGC AATAAAGGTCTGGCACCT) was conducted and specific bands with the expected size of 1.0 kb were obtained in the agarose gel (data not shown), which further confirmed the existence of BBWV-2.A total of 16 marigold leaf samples(7 from Huairou and 9 from Yanqing) with mosaic symptom were collected and tested by RT-PCR with the abovementioned primer pair, and 4 from Huairou were BBWV-2 positive. Sequence analysis showed that these 4 isolates shared 100% nt sequence identity with the former sequenced isolateBBWV-2-marigold. Furthermore, CMV specific primer pair targeting the CP (F: 5-ATGGACAAATCTGGATCTCCCAAT-3/R: 5-CTAAGTCGGG AGCATCCGTGAGAT-3) were designed to detect the existence of CMV in these samples and results showed that all these 16 samples were positive for CMV. To the best of our knowledge, this is the first report of BBWV-2 in marigold in China.These findings will assist investigations on the epidemiology of diseases caused by BBWV2 in China.

Prognostic impacts of extracranial metastasis on non-small cell lung cancer with brain metastasis: A retrospective study based on surveillance, epidemiology, and end results database.

This study was designed to investigate the prognostic value of the number and sites of extracranial metastasis (ECM) in NSCLC patients with BM. NSCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were enrolled in analysis. Patients from 2010 to 2013 were included in the training set and those from 2014 to 2015 in the validation set. ECM sites among different subtypes of NSCLC were compared by Chi-square tests. Kaplan-Meier methods and Cox regression models were performed to analyze survival data. Competing-risks analysis was used to predict cumulative incidence rates for CSS and non-CSS cause. We included 5974 patients in the training cohort and 3561 patients in the validation cohort. Most (nearly 80%) NSCLC patients with BM showed 0-1 involved extracranial organ, with the most and least common ECM organ being bone and distant lymph nodes (DLNs) among all subtypes of NSCLC, respectively. The number of involved extracranial organs was an independent prognostic factor for patients with BM from NSCLC (p < 0.001). Patients with 0-1 ECM had better survival than those with larger number of involved extracranial organs (p < 0.001). Cumulative incidence rates for CSS were increased with the number of ECM raising (p < 0.001). All involved extracranial organs were associated with worse survival (p < 0.05). In patients with single-organ ECM, we observed a better prognosis in lung and bone metastasis, while liver metastasis showed worst survival. But the difference in survival in these patient groups was relatively small. Patients with liver metastasis had higher cumulative incidence rates for CSS than that in patients with lung and bone metastasis (p < 0.05). More extracranial metastases were associated with poor prognosis in NSCLC patients with BM and ECM sites showed limited effect on survival. Tailored treatments would be reasonable for BM patients from NSCLC with different metastasis patterns.

Feasibility study of mitigation and suppression strategies for controlling COVID-19 outbreaks in London and Wuhan.

Recent outbreaks of coronavirus disease 2019 (COVID-19) has led a global pandemic cross the world. Most countries took two main interventions: suppression like immediate lockdown cities at epicenter or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both strategies have their apparent merits and limitations; it becomes extremely hard to conduct one intervention as the most feasible way to all countries. Targeting at this problem, this paper conducted a feasibility study by defining a mathematical model named SEMCR, it extended traditional SEIR (Susceptible-Exposed-Infectious-Recovered) model by adding two key features: a direct connection between Exposed and Recovered populations, and separating infections into mild and critical cases. It defined parameters to classify two stages of COVID-19 control: active contain by isolation of cases and contacts, passive contain by suppression or mitigation. The model was fitted and evaluated with public dataset containing daily number of confirmed active cases including Wuhan and London during January 2020 and March 2020. The simulated results showed that 1) Immediate suppression taken in Wuhan significantly reduced the total exposed and infectious populations, but it has to be consistently maintained at least 90 days (by the middle of April 2020). Without taking this intervention, we predict the number of infections would have been 73 folders higher by the middle of April 2020. Its success requires efficient government initiatives and effective collaborative governance for mobilizing of corporate resources to provide essential goods. This mode may be not suitable to other countries without efficient collaborative governance and sufficient health resources. 2) In London, it is possible to take a hybrid intervention of suppression and mitigation for every 2 or 3 weeks over a longer period to balance the total infections and economic loss. While the total infectious populations in this scenario would be possibly 2 times than the one taking suppression, economic loss and recovery of London would be less affected. 3) Both in Wuhan and London cases, one important issue of fitting practical data was that there were a portion (probably 62.9% in Wuhan) of self-recovered populations that were asymptomatic or mild symptomatic. This finding has been recently confirmed by other studies that the seroprevalence in Wuhan varied between 3.2% and 3.8% in different sub-regions. It highlights that the epidemic is far from coming to an end by means of herd immunity. Early release of intervention intensity potentially increased a risk of the second outbreak.

Staging Alzheimer's Disease in the Brain and Retina of B6.APP/PS1 Mice by Transcriptional Profiling.

Alzheimer's disease (AD) is a common form of dementia characterized by amyloid plaque deposition, tau pathology, neuroinflammation, and neurodegeneration. Mouse models recapitulate some key features of AD. For instance, the B6.APP/PS1 model (carrying human transgenes for mutant forms of APP and PSEN1) shows plaque deposition and neuroinflammation involving both astrocytes and microglia beginning around 4-6 months of age. However, significant tau pathology and neurodegeneration are not apparent in this model even when assessed at old age. Therefore, this model is ideal for studying neuroinflammatory responses to amyloid deposition. Here, RNA sequencing of brain and retinal tissue, generalized linear modeling (GLM), functional annotation followed by validation by immunofluorescence was performed in B6.APP/PS1 mice to determine the earliest molecular changes prior to and around the onset of plaque deposition (2-6 months of age). Multiple pathways were shown to be activated in response to amyloid deposition including the JAK/STAT and NALFD pathways. Putative, cell-specific targets of STAT3, a central component of the JAK/STAT pathway, were identified that we propose provide more precise options for assessing the potential for targeting activation of the JAK/STAT pathway as a treatment for human AD. In the retina, GLM predicted activation of vascular-related pathways. However, many of the gene expression changes comparing B6 with B6.APP/PS1 retina samples occurred prior to plaque onset (2 months of age). This suggests retinal changes in B6.APP/PS1 mice may be an artefact of overexpression of mutant forms of APP and PSEN1 providing limited translatability to human AD. Therefore, caution should be taken when using this mouse model to assess the potential of using the eye as a window to the brain for AD.

Carbon dot-sensitized MoS2 nanosheet heterojunctions as highly efficient NIR photothermal agents for complete tumor ablation at an ultralow laser exposure.

Currently, one of the major hurdles hindering the clinical applications of photothermal therapy (PTT) and photothermal-chemo combination therapy (PCT) is the lack of highly efficient, readily derived, and irradiation-safe photothermal agents in the biologically transparent window. Herein, we report the first design and rational construction of 0D/2D/0D sandwich heterojunctions for greatly enhanced PTT and PCT performances using 0D N-doped carbon dots and 2D MoS2 nanosheets as the assembly units. The well-matching heterojunctions enabled an additional enhancement in NIR absorbance owing to the carrier injection from carbon dots to MoS2 nanosheets, and achieved a much higher photothermal conversion efficiency (78.2%) than that of single NIR-CDs (37.6%) and MoS2 (38.3%) only. In virtue of the heterojunction-based PTT, complete tumor recession without recurrence or pulmonary metastasis was realized at an ultralow and safe laser exposure (0.2 W cm-2) below the skin tolerance irradiation threshold. Furthermore, by taking advantage of the strong X-ray attenuation and effective drug loading capacity of MoS2 nanosheets, the CT imaging-guided PCT was achieved at 0.1 W cm-2, without inducing noticeable toxic side effects. Our findings can substantiate the potential of a novel 0D/2D heterojunction for cancer theranostics.