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BackgroundThe influence of meteorological factors on the transmission and spread of COVID-19 is of interest and has not been investigated. ObjectiveThis study aimed to investigate the associations between meteorological factors and the daily number of new cases of COVID-19 in 9 Asian cities. MethodsPearson correlation and generalized additive modeling (GAM) were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available. ResultsThe Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=–0.565, P

A novel pneumonia-like coronavirus disease (COVID-19) caused by a novel coronavirus named SARS-CoV-2 has swept across China and the world. Public health measures that were effective in previous infection outbreaks (eg, wearing a face mask, quarantining) were implemented in this outbreak. Available multidimensional social network data that take advantage of the recent rapid development of information and communication technologies allow for an exploration of disease spread and control via a modernized epidemiological approach. By using spatiotemporal data and real-time information, we can provide more accurate estimates of disease spread patterns related to human activities and enable more efficient responses to the outbreak. Two real cases during the COVID-19 outbreak demonstrated the application of emerging technologies and digital data in monitoring human movements related to disease spread. Although the ethical issues related to using digital epidemiology are still under debate, the cases reported in this article may enable the identification of more effective public health measures, as well as future applications of such digitally directed epidemiological approaches in controlling infectious disease outbreaks, which offer an alternative and modern outlook on addressing the long-standing challenges in population health.

People across the world have been greatly affected by the ongoing coronavirus disease (COVID-19) pandemic. The high infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hospitals is particularly problematic for recently delivered mothers and currently pregnant women who require professional antenatal care. Online antenatal care would be a preferable alternative for these women since it can provide pregnancy-related information and remote clinic consultations. In addition, online antenatal care may help to provide relatively economical medical services and diminish health care inequality due to its convenience and cost-effectiveness, especially in developing countries or regions. However, some pregnant women will doubt the reliability of such online information. Therefore, it is important to ensure the quality and safety of online services and establish a stable, mutual trust between the pregnant women, the obstetric care providers and the technology vis-a-vis the online programs. Here, we report how the COVID-19 pandemic brings not only opportunities for the development and popularization of online antenatal care programs but also challenges.

Abstract Background This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. Methods This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. Conclusions Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Abstract Background Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer’s disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. Methods The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. Results The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. Conclusions DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders. Graphical Abstract Scheme depicting the possible mechanism by which DNase II deficiency induces cognitive impairment in mice. DNase II deficiency induces tau phosphorylation by regulating kinases CDK5 and CaMKII as well as phosphatase PP2A through accumulation of undigested damaged DNA in the cytoplasm of neurons. Then phosphorylated tau induces synaptic loss, neuroinflammation, and neuronal apoptosis, eventually rendering cognitive impairment in mice.

Abstract Background In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. Methods A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case–control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. Results A significant decrease in ANB (P

Abstract The elderly frequently present impaired blood–brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Abstract The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson’s disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1β, which is subsequently secreted into the extracellular space. This secreted IL-1β then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Abstract One key challenge in the field of topological superconductivity (Tsc) has been the rareness of material realization. This is true not only for the first-order Tsc featuring Majorana surface modes, but also for the higher-order Tsc, which host Majorana hinge and corner modes. Here, we propose a four-step strategy that mathematically derives comprehensive guiding principles for the search and design for materials of general higher-order Tsc phases. Specifically, such recipes consist of conditions on the normal state and pairing symmetry that can lead to a given higher-order Tsc state. We demonstrate this strategy by obtaining recipes for achieving three-dimensional higher-order Tsc phases protected by the inversion symmetry. Following our recipe, we predict that the observed superconductivity in centrosymmetric MoTe2 is a hyrbid-order Tsc candidate, which features both surface and corner modes. Our proposed strategy enables systematic materials search and design for higher-order Tsc, which can mobilize the experimental efforts and accelerate the material discovery for higher-order Tsc phases.

This study aimed to evaluate the distribution of plasma troponin I concentration and establish the 99th percentile reference for hs-cTnI in a hospitalized population without a cardiovascular discharge diagnosis from the Shandong area.

With the rapid development, shared bicycles have gradually become an important part of slow urban traffic in China and have played an important role in satisfying the travel needs and facilitating the transfer of residents. Exploring the spatial and temporal characteristics of the impact of the built environment on shared bike travel is of practical importance to reshape the construction of low-carbon transportation and an urban-friendly cycling environment dominated by slow traffic and public transportation. We analyzed the spatio-temporal characteristics of shared bicycle travel through multi-source big data including Shenzhen's shared bicycle OD data, OSM road network data, Baidu Street View, and POIs and used a multi-scale geographical weighted regression model (MGWR) based on the "5D" index of the built environment to analyze the spatial difference characteristics of the impact of different built environment on shared bicycle flow. The findings of the research indicate that: (1) In terms of time, the shared bicycle flow in the morning and evening peaks of both working and rest days is more significant than that of other periods, and the peak period of the remaining days lags behind that of the working days. (2) In terms of space, the spatial distribution characteristics of the traffic flow of shared bicycles during each peak period exhibit a spatial pattern of "multiple aggregation cores and several extended belts." (3) Significant differences were observed in the impact of various built environmental factors on the flow of shared bicycle travel, among which, employment facility density, enclosure degree and population density had a positive effect in each period; their influences were globally significant; and the remaining factors demonstrated varied characteristics in each period. (4) Factors with significant influence showed different spatial scales in different periods. The spatial changes of employment facility density and enclosure in each period were generally flat; the spatial changes of proximity, density of shopping facilities, and the nearest distance to subway stations in some periods were generally flat; the spatial changes of building continuity and relative walking width were obvious in some periods. Moreover, population density and green vision rate had different spatial characteristics in different periods. This study restores the travel track of shared bicycles, analyzes the spatiotemporal characteristics of shared bicycle travel in multiple periods of working days and rest days and long-term series, and increases micro-built environment factors of subjective perception of people and experience dimension based on existing objective material space environment variables, to explore the spatiotemporal differences of the impact of different built environments on the travel flow of shared bicycles which compensate for the existing shared-bike travel time and space characteristics, build a shortage of environmental impact research, and provide references for the construction of an urban-friendly cycling environment and the creation of a slow walking space.

Abstract Designing an organic polymer photocatalyst for efficient hydrogen evolution with visible and near-infrared (NIR) light activity is still a major challenge. Unlike the common behavior of gradually increasing the charge recombination while shrinking the bandgap, we present here a series of polymer nanoparticles (Pdots) based on ITIC and BTIC units with different π-linkers between the acceptor-donor-acceptor (A-D-A) repeated moieties of the polymer. These polymers act as an efficient single polymer photocatalyst for H2 evolution under both visible and NIR light, without combining or hybridizing with other materials. Importantly, the difluorothiophene (ThF) π-linker facilitates the charge transfer between acceptors of different repeated moieties (A-D-A-(π-Linker)-A-D-A), leading to the enhancement of charge separation between D and A. As a result, the PITIC-ThF Pdots exhibit superior hydrogen evolution rates of 279 µmol/h and 20.5 µmol/h with visible (>420 nm) and NIR (>780 nm) light irradiation, respectively. Furthermore, PITIC-ThF Pdots exhibit a promising apparent quantum yield (AQY) at 700 nm (4.76%).

Abstract Introduction Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC‐A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. Methods Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC‐A measurements in 2014–2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC‐A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. Results Eighty patients were included. LCGM models identified two distinct trajectories of SCC‐A: low‐stable (40%; n = 32) and high‐decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23–10.53], p = 0.019), progression‐free survival (HR [95% CI]: 11.33 [3.19–40.3], p

The composition and content of fatty acids (FAs) and amino acids (AAs) are important nutritional and sensory traits in aquaculture fish. To meet increasing demand while retaining quality, genetic selection in breeding programs is urgently needed to improve these traits. In this study, we performed the genome-wide association study (GWAS) to identify genetic variants and candidate genes potentially linked to FA and AA compositions in grass carp muscle. We focused on key dietary components, including unsaturated FAs and essential AAs. Through profiling of total FA and AA contents, we identified strong positive correlations among the compositions of most FAs and AAs. From our GWAS panel, 4,913,199 high-quality single nucleotide polymorphisms (SNPs) were identified across the genome, of which 32 SNPs linked to 18 candidate genes were significantly associated with FA levels, and 202 SNPs linked to 115 candidate genes associated with AA contents. In addition, we categorized our sequencing population by region and detected allele frequencies of SNPs across four geographic locations. Notably, four FA-associated SNPs and 28 AA-associated SNPs exhibited geographic specificity. These results offered valuable insights into the complex genetic basis of FA and AA metabolism and deposition. Furthermore, this work provides potential genetic markers for selective breeding aimed at enhancing flesh quality in the economically important fish species, grass carp.