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ObjectiveSchizonepeta tenuifolia -Saposhnikovia divaricata (Jingjie-Fangfeng, JF) has been used for years to treat allergic inflammatory skin diseases like atopic dermatitis, but the specific effects and mechanisms of JF are still unclear.PurposeWe aim to investigate the therapeutic effect and mechanism of JF in MC903-induced atopic dermatitis-like model.MethodsJF decoction was subjected to rigorous HPLC and GC analysis. The JF decoction was then freshly prepared and administered to MC903-induced atopic dermatitis -like mice models to investigate its therapeutic effects. Our evaluation focused on several markers of inflammation including the TEWL index, ear thickness, swelling, and specific inflammation indicators such as TSLP, IL33, IgE, and immune cell presence at the lesion sites. We measured Transient Receptor Potential Vanilloid 1 (TRPV1) expression levels through immunofluorescent staining in skin tissue from both atopic dermatitis patients and the MC903-treated mice. Furthermore, TRPV1 expression and macrophage activation markers were measured in LPS/IFN-γ-stimulated Raw264.7 and THP-1 cell models in vitro. Additionally, we developed cell lines that overexpress TRPV1 and investigated how JF treatment affects NF-κB p65 phosphorylation in these cells to understand better the role of TRPV1 in atopic dermatitis.ResultsThe JF decoction met the standards outlined in the Chinese pharmacopeia. The JF decoction significantly alleviated inflammatory skin symptoms and helped restore skin barrier function. Additionally, it reduced the levels of IgE and pro-inflammatory cytokines TSLP, IL-33, and IL-4. There was also a noticeable decrease in mast cell infiltration and degranulation. Notably, JF decoction reduced infiltrated macrophages with limited affection on T cell infiltration. It also decreased F4/80+/TRPV1+ cells in atopic dermatitis mice and TRPV1 expression in LPS/IFNγ-stimulated microphages. Additionally, we observed that CD68+/TRPV1+ cells increased in human atopic dermatitis tissue. Further studies showed that JF water extract (JF-WE) suppressed TRPV1 expression in macrophages, potentially by affecting NF-κB p65 phosphorylation rather than the JAK-STAT6 pathway.ConclusionThis study offers initial evidence of the effectiveness of JF-WE in suppressing inflammation in atopic dermatitis. The therapeutic effect might stems from its ability to downregulate TRPV1 expression and subsequent NF-κB p65 phosphorylation in macrophages.

Abstract Background Public health workers are a crucial part of the health workforce, particularly during the coronavirus disease (COVID-19) pandemic. They play an important role in achieving universal health coverage and sustainable development goals. Human resources in public health in China are in short supply, their distribution is unequal, and their turnover rate is high. A discrete choice experiment (DCE) was applied to investigate preventive medicine students’ preferred job choice criteria and trends in trade-offs by calculating the marginal rate of substitution between these criteria. This study identified the properties of jobs primarily selected by preventive medicine students and estimated the monetary value of each attribute. Methods Based on discussions and in-depth interviews with preventive medicine students and a literature review, we developed a DCE that assessed how students’ stated preferences for a certain choice were influenced by several job attributes, including location, salary, bianzhi, career development opportunities, working environment, and workload. We applied this DCE to preventive medicine students in Shandong Province, China, using a brief, structured questionnaire. Conditional logit models were used to estimate the utility of each job’s attributes. Willingness to pay (WTP) was estimated as the ratio of the value of the coefficient of interest to the negative value of the cost attribute. Results A total of 307 respondents completed the questionnaire, and 261 passed the internal consistency test. All the attributes were statistically significant. Career development opportunities and work locations were the most important factors for the respondents. Preference heterogeneity existed among respondents, e.g., 3-year medical education college students placed a higher value on jobs with bianzhi compared to 5-year medical education college students. Furthermore, rural students’ WTP for a job located in the county or city is much lower than that of urban students. Conclusions The heterogeneity of attributes indicates the complexity of job preferences. Monetary and nonmonetary job characteristics significantly influenced the job preferences of preventive medicine students in China. A more effective policy intervention to attract graduates to work in rural areas should consider both job incentives and the backgrounds of preventive medicine graduates.

Continuous advances in concentrating photovoltaic (CPV) panel efficiency are increasingly affected by cell temperature. Improving PV panel cooling performance is critical. This application optimizes the internal flow channel structure of PV panel cooling systems using topology optimization techniques like multi-objective and multi-stage optimization with penalty factors. Three-dimensional CFD simulation is used to compare the heat transfer performance of topology optimized channel cooling configuration and traditional straight channel cooling configuration for photovoltaic panel systems. Effects of inlet flow rates, concentration ratios, and other parameters on cooling performance are investigated. Results show the topology optimized flow channel configuration has better cooling than the straight channel. At different concentration ratios, the solar cell temperature reduces 13.85%–23.45%. The optimized application also has lower inlet and outlet pressure drops for the same operating conditions, requiring less external power. Compared to the straight channel, the topology optimized flow channel increases net PV system output power 3.00%–19.37% at different concentration ratios. Applying topology optimization provides new ideas for optimizing PV cooling system designs.

ABSTRACTSARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analogue, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for SARS-CoV-2 to methylate the N7 position of viral 5’-RNA guanine cap. The assay is universal and suitable for any SAM-dependent viral MTases such as the SARS-CoV-2 NSP16/NSP10 MTase complex and the NS5 MTase of Zika virus (ZIKV). Pilot screening demonstrated that the HTS assay was very robust and identified two candidate inhibitors, NSC 111552 and 288387. The two compounds inhibited the FL-NAH binding to the NSP14 MTase with low micromolar IC50. We used three functional MTase assays to unambiguously verified the inhibitory potency of these molecules for the NSP14 N7-MTase function. Binding studies indicated that these molecules are bound directly to the NSP14 MTase with similar low micromolar affinity. Moreover, we further demonstrated that these molecules significantly inhibited the SARS-CoV-2 replication in cell-based assays at concentrations not causing cytotoxicity. Furthermore, NSC111552 significantly synergized with known SARS-CoV-2 drugs including nirmatrelvir and remdesivir. Finally, docking suggested that these molecules bind specifically to the SAM-binding site on the NSP14 MTase. Overall, these molecules represent novel and promising candidates to further develop broad-spectrum inhibitors for the management of viral infections.

BackgroundIntracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurological conditions, the deposition of extracellular matrix (ECM) molecules is a prominent obstacle for regenerative processes and an enhancer of neuroinflammation. Whether ECM molecules alter in composition after ICH, and which ECM members may inhibit repair, remain largely unknown in hemorrhagic stroke.MethodsThe collagenase-induced ICH mouse model and an autopsied human ICH specimen were investigated for expression of ECM members by immunofluorescence microscopy. Confocal image z-stacks were analyzed with Imaris 3D to assess the association of immune cells and ECM molecules. Sections from a mouse model of multiple sclerosis were used as disease and staining controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs).ResultsAmong the lectican chondroitin sulfate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in murine ICH. Fibrinogen, fibronectin and heparan sulfate proteoglycan (HSPG) were also elevated after murine ICH while thrombospondin and tenascin-C was not. Confocal microscopy with Imaris 3D rendering co-localized neurocan, fibrinogen, fibronectin and HSPG molecules to Iba1+ microglia/macrophages or GFAP+ astrocytes. Marked differentiation from the multiple sclerosis model was observed, the latter with high versican-V1 and negligible neurocan. In culture, purified neurocan inhibited adhesion and process outgrowth of OPCs, which are early steps in myelination in vivo. The prominent expression of neurocan in murine ICH was corroborated in human ICH sections.ConclusionICH caused distinct alterations in ECM molecules. Among CSPG members, neurocan was selectively upregulated in both murine and human ICH. In tissue culture, neurocan impeded the properties of oligodendrocyte lineage cells. Alterations to the ECM in ICH may adversely affect reparative outcomes after stroke.

Stroke is the second leading cause of death worldwide and has two major subtypes: ischemic stroke and hemorrhagic stroke. Neuroinflammation is a pathological hallmark of ischemic stroke and intracerebral hemorrhage (ICH), contributing to the extent of brain injury but also in its repair. Neuroinflammation is intricately linked to the extracellular matrix (ECM), which is profoundly altered after brain injury and in aging. In the early stages after ischemic stroke and ICH, immune cells are involved in the deposition and remodeling of the ECM thereby affecting processes such as blood-brain barrier and cellular integrity. ECM components regulate leukocyte infiltration into the central nervous system, activate a variety of immune cells, and induce the elevation of matrix metalloproteinases (MMPs) after stroke. In turn, excessive MMPs may degrade ECM into components that are pro-inflammatory and injurious. Conversely, in the later stages after stroke, several ECM molecules may contribute to tissue recovery. For example, thrombospondin-1 and biglycan may promote activity of regulatory T cells, inhibit the synthesis of proinflammatory cytokines, and aid regenerative processes. We highlight these roles of the ECM in ischemic stroke and ICH and discuss their potential cellular and molecular mechanisms. Finally, we discuss therapeutics that could be considered to normalize the ECM in stroke. Our goal is to spur research on the ECM in order to improve the prognosis of ischemic stroke and ICH.

Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol’s ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol’s role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol’s promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.

In this article, a methodology is proposed to implement fractional-order analog wavelet filters in the frequency domain. Under the proposed scheme, the fractional-order transfer function of the linear time-invariant system is used to approximate the Gaussian-like wavelet functions. Firstly, we construct a causal, stable, and physically achievable fractional-order mathematical approximation model. Then, the fractional-order mathematical approximation model is transformed into an optimization problem, and a hybrid particle swarm optimization algorithm is exploited to find its global optimal solution. At the same time, constraint terms are introduced to ensure the desired stability. The simulation results show that the fractional-order analog wavelet filters have higher approximation accuracy than the traditional integer-order analog wavelet filters. Furthermore, fractional-order analog wavelet filters can provide more precise control of the stopband attenuation rate, which is a key issue for many engineering applications.

Timely short-term spatial air quality forecasting is essential for monitoring and prevention in urban agglomerations, providing a new perspective on joint air pollution prevention. However, a single model on air pollution forecasting or spatial correlation analysis is insufficient to meet the strong demand. Thus, this paper proposed a complex real-time monitoring and decision-making assistance system, using a hybrid forecasting module and social network analysis. Firstly, before an accurate forecasting module was constructed, text sentiment analysis and a strategy based on multiple feature selection methods and result fusion were introduced to data preprocessing. Subsequently, CNN-D-LSTM was proposed to improve the feature capture ability to make forecasting more accurate. Then, social network analysis was utilized to explore the spatial transporting characteristics, which could provide solutions to joint prevention and control in urban agglomerations. For experiment simulation, two comparative experiments were constructed for individual models and city cluster forecasting, in which the mean absolute error decreases to 7.8692 and the Pearson correlation coefficient is 0.9816. For overall spatial cluster forecasting, related experiments demonstrated that with appropriate cluster division, the Pearson correlation coefficient could be improved to nearly 0.99.

Abstract High-pressure multistage centrifugal pumps have been widely used in modern industry and required low vibration and noise. In this study, modal analysis of the rotor system of a seven-stage centrifugal pump was carried out numerically by introducing fluid force to ensure that the centrifugal pump would not resonate. A vibration test bench was established to investigate the characteristics with flow rates of 0.8Qd, 1.0Qd, and 1.2Qd, and the vibration data of ten measuring points were collected. The period of the vibration at the bearing was found to be around 20 ms and the period was related to the shaft frequency (SF) and the blade passing frequency (BPF). The vibration of the pump casing was mainly determined by the SF, two times the SF, and two times the BPF. Mechanical motion is the main factor causing pump vibration, and fluid unstable motion is also an important cause.

Numerous studies have established that the hypoxic conditions within ovarian follicles induce apoptosis in granulosa cells (GCs), a pivotal hallmark of follicular atresia. Melatonin (N-acetyl-5-methoxytryptamine, MT), a versatile antioxidant naturally present in follicular fluid, acts as a safeguard for maintaining GCs’ survival during stress exposure. In this study, we unveil an innovative protective mechanism of melatonin against hypoxia-triggered GC apoptosis by selectively inhibiting mitochondrial ROS (mtROS) generation. Specifically, under hypoxic conditions, a gradual accumulation of mitochondrial ROS occurred, consequently activating the JNK-FOXO1 pathway, and driving GCs toward apoptosis. The blocking of JNK or FOXO1 diminished hypoxia-induced GC apoptosis, but this effect was nullified in the presence of GSH, indicating that mtROS instigates apoptosis through the JNK-FOXO1 pathway. Consistent with this, hypoxic GCs treated with melatonin exhibited decreased levels of mtROS, reduced JNK-FOXO1 activation, and mitigated apoptosis. However, the protective capabilities of melatonin were attenuated upon inhibiting its receptor MTNR1B, accompanied by the decreased expression of antioxidant genes. Notably, SOD2, a key mitochondrial antioxidant gene modulated by the melatonin–MTNR1B axis, effectively inhibited the activation of mtROS-JNK-FOXO1 and subsequent apoptosis, whereas SOD2 knockdown abrogated the protective role of melatonin in hypoxic GCs. In conclusion, our study elucidates that melatonin, through MTNR1B activation, fosters SOD2 expression, effectively quelling mtROS-JNK-FOXO1-mediated apoptosis in follicular GCs under hypoxic stress.

Shrinkage cracks severely affect the safety of wood structures. Therefore, the moisture stress distribution of shrinkage cracks should be analyzed, and the interface crack depth of wood components predicted. In this paper, the equilibrium conditions, physical conditions, geometric conditions, and coordination equations of the disk humidity stress under a moisture content gradient Δw are deduced by referring to the elastic analytical solution model of temperature stress. Moreover, the humidity stress distribution equation is established, which is verified via the finite element method. The critical water content and shrinkage crack depth prediction models are further deduced based on the humidity stress distribution. The usability of the model is further verified using the test data of actual engineered wood components. The results demonstrate that the moisture stress is not determined by the initial moisture content Wi, equilibrium moisture content We, or member size but by moisture content gradient Δw. The shrinkage crack prediction model of wood components in cross-section can be applied to actual engineering prediction to provide a theoretical basis for the reinforcement measures and safety evaluation of wood structures.

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.

Sensorineural deafness becomes an inevitable worldwide healthy problem, yet the current curative therapy is limited. Emerging evidences demonstrate mitochondrial dysfunction plays a vital role of in the pathogenesis of deafness. Reactive oxygen species (ROS)-induced mitochondrial dysfunction combined with NLRP3 inflammasome activation is involved in cochlear damage. Autophagy not only clears up undesired proteins and damaged mitochondria (mitophagy), but also eliminate excessive ROS. Appropriate enhancement of autophagy can reduce oxidative stress, inhibit cell apoptosis, and protect auditory cells. In addition, we further discuss the interplays linking ROS generation, NLRP3 inflammasome activation, and autophagy underlying the pathogenesis of deafness, including ototoxic drugs-, noise- and aging-related hearing loss.

Over the past few years, chaotic image encryption has gained extensive attention. Nevertheless, the current studies on chaotic image encryption still possess certain constraints. To break these constraints, we initially created a two-dimensional enhanced logistic modular map (2D-ELMM) and subsequently devised a chaotic image encryption scheme based on vector-level operations and 2D-ELMM (CIES-DVEM). In contrast to some recent schemes, CIES-DVEM features remarkable advantages in several aspects. Firstly, 2D-ELMM is not only simpler in structure, but its chaotic performance is also significantly better than that of some newly reported chaotic maps. Secondly, the key stream generation process of CIES-DVEM is more practical, and there is no need to replace the secret key or recreate the chaotic sequence when handling different images. Thirdly, the encryption process of CIES-DVEM is dynamic and closely related to plaintext images, enabling it to withstand various attacks more effectively. Finally, CIES-DVEM incorporates lots of vector-level operations, resulting in a highly efficient encryption process. Numerous experiments and analyses indicate that CIES-DVEM not only boasts highly significant advantages in terms of encryption efficiency, but it also surpasses many recent encryption schemes in practicality and security.

Long-term exposure to air pollution will pose a serious threat to human health. Accurate prediction can help people reduce exposure risks and promote environmental pollution control. However, most previous studies have ignored the spatial spillover of air pollution, i.e., that the current region’s air quality is also correlated with that of geographically adjacent areas. Therefore, this paper proposes an innovative spatiotemporal hybrid early warning system based on adaptive feature extraction and improved fuzzy cognition maps. Firstly, a spatial spillover analysis model based on the Moran index and local gravitational clustering was proposed to capture the diffusion and concentration characteristics of air pollution between regions. Then, an adaptive feature extraction model based on an optimized Hampel filter was put forward to process and correct the outliers in the original series. Finally, a hesitant fuzzy information optimized fuzzy cognitive maps model was proposed to forecast the air quality of urban agglomeration. The experimental results show that the air quality forecasting accuracy of urban agglomerations can be significantly improved when the geographical conditions and other interactions among cities are comprehensively considered, and the proposed model outperformed other benchmarks and can be used as a powerful analytical tool during urban agglomeration air quality management.

Estimating the relationships between individuals is one of the fundamental challenges in many fields. In particular, relationship.ip estimation could provide valuable information for missing persons cases. The recently developed investigative genetic genealogy approach uses high-density single nucleotide polymorphisms (SNPs) to determine close and more distant relationships, in which hundreds of thousands to tens of millions of SNPs are generated either by microarray genotyping or whole-genome sequencing. The current studies usually assume the SNP profiles were generated with minimum errors. However, in the missing person cases, the DNA samples can be highly degraded, and the SNP profiles generated from these samples usually contain lots of errors. In this study, a machine learning approach was developed for estimating the relationships with high error SNP profiles. In this approach, a hierarchical classification strategy was employed first to classify the relationships by degree and then the relationship types within each degree separately. As for each classification, feature selection was implemented to gain better performance. Both simulated and real data sets with various genotyping error rates were utilized in evaluating this approach, and the accuracies of this approach were higher than individual measures; namely, this approach was more accurate and robust than the individual measures for SNP profiles with genotyping errors. In addition, the highest accuracy could be obtained by providing the same genotyping error rates in train and test sets, and thus estimating genotyping errors of the SNP profiles is critical to obtaining high accuracy of relationship estimation.

Sertraline (SER) is one of the most commonly detected antidepressants in the aquatic environment that can negatively affect aquatic organisms at low concentrations. Despite some knowledge on its acute toxicity to fish, the effects of chronic SER exposure remain poorly understood along with any underlying mechanisms of SER-induced toxicity. To address this knowledge gap, the effects of chronic exposure to three SER concentrations from low to high were investigated in zebrafish. Juvenile zebrafish were exposed to three concentrations of 1, 10, or 100 μg/L of SER for 28 d, after which indicators of oxidative stress and neurotoxicity in the brain were measured. Superoxide dismutase (SOD) activity was significantly enhanced by SER at 1 up to 100 μg/L, and catalase (CAT) activity was significantly induced by SER at 1 or 10 μg/L. The activity of acetylcholinesterase (AChE) was significantly induced by 10 and 100 μg/L of SER, and the serotonin (5-HT) level was significantly increased by all three concentrations of SER. To ascertain mechanisms of SER-induced toxicity, transcriptomics was conducted in the brain of zebrafish following 100 μg/L SER exposure. The molecular signaling pathways connected with circadian system and the immune system were significantly altered in the zebrafish brain. Based on transcriptomic data, the expression levels of six circadian clock genes were measured, and three genes were significantly altered in relative abundance in fish from all experimental treatments with SER, including cryptochrome circadian regulator 2 (cry2), period circadian clock 2 (per2), and period circadian clock 3 (per3). We hypothesize that the circadian system may be related to SER-induced neurotoxicity and oxidative stress in the central nervous system. This study reveals potential mechanisms and key events (i.e., oxidative stress and neurotoxicity) associated with SER-induced toxicity, and improves understanding of the molecular and biochemical pathways putatively perturbed by SER.

Abstract Protein splicing is a post-translational process by which an intein catalyzes its own excision from flanking polypeptides, or exteins, concomitant with extein ligation. Many inteins have nested homing endonuclease domains that facilitate their propagation into intein-less alleles, whereas other inteins lack the homing endonuclease (HEN) and are called mini-inteins. The mini-intein that interrupts the DNA PolII of Pyrococcus horikoshii has a linker region in place of the HEN domain that is shorter than the linker in a closely related intein from Pyrococcus abyssi. The P. horikoshii PolII intein requires a higher temperature for catalytic activity and is more stable to digestion by the thermostable protease thermolysin, suggesting that it is more rigid than the P. abyssi intein. We solved a crystal structure of the intein precursor that revealed a domain-swapped dimer. Inteins found as domain swapped dimers have been shown to promote intein-mediated protein alternative splicing, but the solved P. horikoshii PolII intein structure has an active site unlikely to be catalytically competent.

Background: Leukopenia is one of the side effects of radiotherapy and chemotherapy. Diyushengbai tablet (DYT) is used to prevent and treat leukopenia caused by various reasons. A meta-analysis was performed to systematically analyze the therapeutic effects of DYT on preventing and treating leukopenia caused by radiotherapy and chemotherapy.Objectives: This study aimed to systematically evaluate the efficacy and safety of DYT in preventing and treating leukopenia caused by radiotherapy and chemotherapy.Methods: We performed a comprehensive literature search of electronic databases such as PubMed, The Cochrane Library, China Knowledge Network (CNKI), China Biomedical Literature Database (CBM), Wanfang Data Knowledge Service Platform, and VIP, through November of 2021. The scanning reports deadline is until November 2021. The bias risk evaluation criteria developed by the Cochrane collaborative organization were used to evaluate the literature quality of the included studies. The RevMan5.4 software was used to analyze the data, and the Stata16.0 was used to perform the Egger test.Results: After selecting all the databases, a total of 41 reports which involved 3,793 cases were analyzed. Meta-analysis showed that DYT could significantly reduce the white blood cell (WBC) suppression caused by radiotherapy and chemotherapy and improve the patients’ WBC counts and neutrophils, compared with the efficacy of other oral WBC-elevating drugs such as Leucogen tablets and Batilol tablets and additional utilization of granulocyte colony-stimulating factor (G-CSF). The results of meta-analysis showed that for preventive medication purpose, the overall incidence of leukocyte suppression was [RR = 0.74, 95%CI (0.59, 0.92), p = 0.006], and the white blood cell count was [MD = 1.12, 95%CI (0.95, 1.29), p < 0.00001]; while for therapeutic purpose, the incidence of overall leukocyte suppression was [RR = 0.61, 95%CI (0.38, 0.95), p = 0.03], and the white blood cell count was [MD = 1.20, 95%CI (0.77, 1.62), p < 0.00001]. More importantly, the additional use of DYT can reduce the application amount of G-CSF. The results showed that the application of G-CSF can be reduced by an average of 1.57 from the beginning of treatment to return normal white blood cells around 2.23 in two cycles of chemotherapy.Conclusion: DYT is more effective in preventing and treating leukopenia caused by radiotherapy and chemotherapy than other oral WBC-elevating drugs, which have a high clinical value.

Single-cell RNA-sequencing (scRNA-seq) technologies enable the measurements of gene expressions in individual cells, which is helpful for exploring cancer heterogeneity and precision medicine. However, various technical noises lead to false zero values (missing gene expression values) in scRNA-seq data, termed as dropout events. These zero values complicate the analysis of cell patterns, which affects the high-precision analysis of intra-tumor heterogeneity. Recovering missing gene expression values is still a major obstacle in the scRNA-seq data analysis. In this study, taking the cell heterogeneity into consideration, we develop a novel method, called single cell Gauss–Newton Gene expression Imputation (scGNGI), to impute the scRNA-seq expression matrices by using a low-rank matrix completion. The obtained experimental results on the simulated datasets and real scRNA-seq datasets show that scGNGI can more effectively impute the missing values for scRNA-seq gene expression and improve the down-stream analysis compared to other state-of-the-art methods. Moreover, we show that the proposed method can better preserve gene expression variability among cells. Overall, this study helps explore the complex biological system and precision medicine in scRNA-seq data.

Silk fibroin (SF) is considered biocompatible and biodegradable for osteochondral repair. However, it lacks a bioactive domain for cell adhesion, proliferation and differentiation, limiting its therapeutic efficacy. To revamp SF as a biomimicking and bioactive microenvironment to regulate cell behaviours, we engineered an elastin-like polypeptide (ELP, Val-Pro-Gly-Xaa-Gly) to modify SF fibers via simple and green dehydrothermal (DHT) treatment. Our results demonstrated that the ELP successfully bound to SF, and the scaffold was reinforced by the fusion of the silk fiber intersections with ELP (S-ELP-DHT) via the DHT treatment. Both bone mesenchymal stem cells (BMSCs) and chondrocytes exhibited improved spreading and proliferation on the S-ELP-DHT scaffolds. The ex vivo and in vivo experiments further demonstrated enhanced mature bone and cartilage tissue formation using the S-ELP-DHT scaffolds compared to the naked SF scaffolds. These results indicated that a recombinant ELP-modified silk scaffold can mimic three-dimensional (3D) cell microenvironment, and improve bone and cartilage regeneration. We envision that our scaffolds have huge clinical potential for osteochondral repair.

ObjectiveThe management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA.MethodsClinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated 0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%.ConclusionCsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.

Matrix metalloproteinases (MMPs) are physiologically expressed in the central nervous system in neurons, astrocytes and microglia, and their aberrant elevation contributes to a number of diseases. Amongst the MMP members, MMP−9 has generated considerable attention because of its possible involvement in inflammatory responses, blood-brain barrier permeability, the regulation of perineuronal nets, demyelination, and synaptic long-term potentiation. Emerging evidence indicate an association between MMP−9 and the syndrome of depression. This review provides an updated and comprehensive summary of the probable roles of MMP−9 in depression with an emphasis on the mechanisms and potential of MMP−9 as a biomarker of depression.

Abstract Background In December 2019, a pneumonia caused by SARS-CoV-2 emerged in Wuhan, China and has rapidly spread around the world since then. This study is to explore the patient characteristics and transmission chains of COVID-19 in the population of Gansu province, and support decision-making. Methods We collected data from Gansu Province National Health Information Platform. A cross-sectional study was conducted, including patients with COVID-19 confirmed between January 23 and February 6, 2020, and analyzed the gender and age of the patients. We also described the incubation period, consultation time and sources of infection in the cases, and calculated the secondary cases that occurred within Gansu for each imported case. Results We found thirty-six (53.7%) of the patients were women and thirty-one (46.3%) men, and the median ages were 40 (IQR 31–53) years. Twenty-eight (41.8%) of the 67 cases had a history of direct exposure in Wuhan. Twenty-five (52.2%) cases came from ten families, and we found no clear reports of modes of transmission other than family clusters. The largest number of secondary cases linked to a single source was nine. Conclusion More women than men were diagnosed with COVID-19 in Gansu Province. Although the age range of confirmed cases of COVID-19 in Gansu Province covered almost all age groups, most patients with confirmed COVID-19 tend to be middle aged persons. The most common suspected mode of transmission was through family cluster. Gansu and other settings worldwide should continue to strengthen the utilization of big data in epidemic control.

Power amplifiers (PAs) are widely used in RF broadcasting applications. However, they exhibit nonlinear behavior and deteriorate the quality of transmitted signals. Digital predistortion (DPD) is developed to linearize the distortion generated by PAs. Due to the contradiction between modeling precision and complexity, to reduce the complexity and ensure comparable performance, it is necessary to determine an appropriate or optimized structure before applying DPD. Heuristic method is a good method to solve such multivariate problems with a considerable large search domain. In this paper, a novel approach to determine the structure of DPD based on heuristic method is proposed, including the enhanced hill-climbing (EHC) with stronger global search ability and enhanced genetic algorithm (EGA). Ridge regression is introduced to ensure the correctness of the search direction. Besides, orthogonal matching pursuit is used to further reduce the basis number while keeping good performance. The validation of the proposed techniques on a Doherty PA using generalized memory polynomial (GMP) model demonstrates the capability to efficiently find the dimensions of an appropriate GMP model. As shown by the convergence curve and the final model performance, the model searched by the proposed method has satisfactory results, and achieves a good balance between complexity and performance.

To treat various cancers, including lung cancer, chemotherapy requires the systematic administering of chemotherapy. The chemotherapeutic effectiveness of anticancer drugs has been enhanced by polymer nanoparticles (NPs), according to new findings. As an outcome, we have developed biodegradable triblock poly(ethylene glycol)–poly(ε-caprolactone)–poly(ethylene glycol) (PEG–PCL–PEG, PECE) polymeric NPs for the co-delivery of sorafenib (SORA) and crizotinib (CRIZ) and investigated their effect on lung cancer by in vitro and in vivo. There is little polydispersity in the SORA–CRIZ@NPs, an average size of 30.45 ± 2.89 nm range. A steady release of SORA and CRIZ was observed, with no burst impact. The apoptosis rate of SORA–CRIZ@NPs was greater than that of free drugs in 4T1 and A549 cells. Further, in vitro cytotoxicity of the polymeric NPs loaded with potential anticancer drugs was more quickly absorbed by cancer cells. On the other hand, compared to free drugs (SORA + CRIZ), SORA + CRIZ@NPs showed a substantial reduction of tumor development, longer survival rate, and a lowered side effect when delivered intravenously to nude mice xenograft model with 4T1 cancer cells. TUNEL positivity was also increased in tumor cells treated with SORA–CRIZ@NPs, demonstrating the therapeutic effectiveness. SORA–CRIZ@NPs might be used to treat lung cancer soon, based on the results from our new findings.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high rates of mortality and morbidity. It induces cell death that is responsible for neurological deficits postinjury. There are no therapies that effectively mitigate cell death to treat ICH. This review aims to summarize our knowledge of ICH-induced cell death with a focus on apoptosis and necrosis. We also discuss the involvement of ICH in recently described modes of cell death including necroptosis, pyroptosis, ferroptosis, autophagy, and parthanatos. We summarize treatment strategies to mitigate brain injury based on particular cell death pathways after ICH.

Multidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without the need for cofactors or external energy, resulting in joining of extein fragments. Inteins are present in many organisms, including human pathogens such as Mycobacterium tuberculosis, Cryptococcus neoformans, C. gattii, and Aspergillus fumigatus. Because intein elements are not present in human genes, they are attractive drug targets to develop antifungals and antibiotics. Thus far, a few inhibitors of intein splicing have been reported. Metal-ions such as Zn2+ and Cu2+, and platinum-containing compound cisplatin inhibit intein splicing in M. tuberculosis and C. neoformans by binding to the active site cysteines. A small-molecule inhibitor 6G-318S and its derivative 6G-319S are found to inhibit intein splicing in C. neoformans and C. gattii with a MIC in nanomolar concentrations. Inteins have also been used in many other applications. Intein can be used in activating a protein inside a cell using small molecules. Moreover, split intein can be used to deliver large genes in experimental gene therapy and to kill selected species in a mixed population of microbes by taking advantage of the toxin-antitoxin system. Furthermore, split inteins are used in synthesizing cyclic peptides and in developing cell culture model to study infectious viruses including SARS-CoV-2 in the biosafety level (BSL) 2 facility. This mini-review discusses the recent research developments of inteins in drug discovery and therapeutic research.

Air pollution forecasting plays a pivotal role in environmental governance, so a large number of scholars have devoted themselves to the study of air pollution forecasting models. Although numerous studies have focused on this field, they failed to consider fully the linear feature, non-linear feature, and fuzzy features contained in the original series. To fill this gap, a new combined system is built to consider features in the original series and accurately forecast PM2.5 concentration, which incorporates an efficient data decomposition strategy to extract the primary features of the PM2.5 concentration series and remove the noise component, and five forecasting models selected from three types of models to obtain the preliminary forecasting results, and a multi-objective optimization algorithm to combine the prediction results to produce the final prediction values. Empirical studies results indicated that in terms of RMSE the developed combined system achieves 0.652 6%, 0.810 1%, and 0.775 0% in three study cities, respectively. Compared to other prediction models, the RMSE improved by 60% on average in the study cities.

Background: Multinational comparative study of the relation of self-rated health (SRH) with health behavior and chronic disease can ease our perception of differences in health factors between countries. We aimed to compare the relation of SRH with health behavior and chronic disease. Methods: We attempted to analyze larger data obtained from 2010 East-Asian-Social-Survey and to compare the situation of China, Japan, South Korea, and Taiwan (Special administrative region of China). As these are neighboring regions having both similarities and differences in socio-demographic aspects as well as environment and cultures. The study was composed of 10,137 participants. Univariate and multiple regression analyses were employed to estimate the Odds Ratio (OR) and 95% Confidence intervals (CI) for SRH and health-related behavior, sociodemographic, chronic disease variables. Results: The number of individuals reporting Good SRH was 6,648, with China having the higher proportion (P=

In this letter, we consider a new two-component system. By its reciprocal relation with the first negative flow in the AKNS hierarchy, we construct three Darboux-Bäcklund transformations for the new system and obtain some soliton-like solutions.

Conventional analysis methods cannot fully meet the business needs of power grids. At present, several artificial intelligence (AI) projects in a single business field are competing with each other, and the interfaces between the systems lack unified specifications. Therefore, it is imperative to establish a comprehensive service platform. In this paper, an AI platform framework for power fields is proposed; it adopts the deep learning technology to support natural language processing and computer vision services. On one hand, it can provide an algorithm, a model, and service support for power- enterprise applications, and on the other hand, it can provide a large number of heterogeneous data processing, algorithm libraries, intelligent services, model managements, typical application scenarios, and other services for different levels of business personnel. The establishment of the platform framework could break data barrier, improve portability of technology, avoid the investment waste caused by repeated constructions, and lay the foundation for the construction of “platform + application + service” ecological chain.

ABSTRACTMany flaviviruses including the Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, Yellow Fever virus, and Japanese encephalitis virus are significant human pathogens, unfortunately without any specific therapy. Here, we demonstrate that methylene blue, an FDA-approved drug, is a broad-spectrum and potent antiviral against Zika virus and Dengue virus both in vitro and in vivo. We found that methylene blue can considerably inhibit the interactions between viral protease NS3 and its NS2B co-factor, inhibit viral protease activity, inhibit viral growth, protect 3D mini-brain organoids from ZIKV infection, and reduce viremia in a mouse model. Mechanistic studies confirmed that methylene blue works in both entry and post entry steps, reduces virus production in replicon cells and inhibited production of processed NS3 protein. Overall, we have shown that methylene blue is a potent antiviral for management of flavivirus infections, particularly for Zika virus. As an FDA-approved drug, methylene blue is well-tolerated for human use. Therefore, methylene blue represents a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses.

This paper proposes two novel vector decomposed neural network models for behavioral modeling and digital predistortion (DPD) of radio-frequency (RF) power amplifiers (PAs): vector decomposed long short-term memory (VDLSTM) model and simplified vector decomposed long short-term memory (SVDLSTM) model. The proposed VDLSTM model is a variant of the classic long short-term memory (LSTM) model that can model long-term memory effects. To comply with the physical mechanism of RF PAs, VDLSTM model only conducts nonlinear operations on the magnitudes of the input signals, while the phase information is recovered by linear weighting operations on the output of the LSTM cell. Furthermore, this study modifies the LSTM cell by adding phase recovery operations inside the cell and replacing the original hidden state with the output magnitudes that are recovered with phase information. With the modified LSTM cell, a low-complexity SVDLSTM model is proposed. The experiment results show that the proposed VDLSTM model can achieve better linearization performance compared with the state-of-the-art models when linearizing PAs with wideband inputs. Besides, in wideband scenarios, SVDLSTM model with much fewer parameters can present comparable linearzation performance compared to VDLSTM model.

This article presents two novel neural network models based on recurrent neural network (RNN) for radio frequency power amplifiers (RF PAs): instant gated recurrent neural network (IGRNN) model and instant gated implict recurrent neural network (IGIRNN) model. In IGRNN model, two state control units are introduced to ensure the linear transmission of hidden state and solve the problem of vanishing gradients of RNN model. In contrast with conventional RNN model, IGRNN can better describe the long-term memory effect of power amplifier, more in line with the physical distortion characteristics of power amplifier. Furthermore the instantaneous gates are used to express the input information implicitly to reduce the redundancy of the input information, and a simpler IGIRNN model is proposed. The complexity analysis indicates that the proposed models have significantly lower complexity than other RNN-based variant structures. A wideband Doherty RF PA excited by 100MHz and 120MHz OFDM signals was employed to evaluate the performance. Extensive experimental results reveal that the proposed IGRNN and IGIRNN models can achieve better linearization performance compared with RNN model and traditional GMP model, and have comparable performance with lower computational complexity compared with the state-of-the-art RNN-based variant models, such as gated recurrent unit (GRU) model.

In this paper, we consider the inviscid limit of a nonhomogeneous incompressible Navier–Stokes system with a slip-without-friction boundary condition. We study the convergence in strong norms for a solution and obtain the convergence rate in space W2,p(Ω) when the boundary is flat. We need to establish the uniform bound of the solution in space W3,p(Ω), and the key of proofs is to obtain a priori estimation of ∂tu in space W1,p(Ω).

To address the limitations of conventional stereo-digital image correlation (DIC) on measuring complex objects, a continuous-view multi-camera DIC (MC-DIC) system and its two forms of camera arrangement are introduced. Multiple cameras with certain overlapping field of view are calibrated simultaneously to form an overall system for measuring the continuous full-surface deformation. The bending experiment of coral aggregate concrete beam and the axial compression experiment of timber column are conducted to verify the capability of continuous-view MC-DIC in deformation measurement of civil components with large slenderness ratio and large curvature, respectively. The obtained deformation data maintain good consistency with the displacement transducer and strain gauge. Results indicate that the continuous-view MC-DIC is a reliable 3D full-field measurement approach in civil measurements.

Background: Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear.Methods: Bone marrow mononuclear cells from 10 patients newly diagnosed with aplastic anemia and 10 healthy volunteers were collected and cultured together with stanozolol, danazol, or blank control separately for marrow colony assays. K562 cell lines that had been incubated with stanozolol, danazol, or blank control were tested for erythroid or megakaryocytic differentiation. Meanwhile, CB6F1/Crl mice were injected with 1 × 106 C57BL/6 donor-originated lymphocytes after irradiation with 5 Gy total body irradiation to establish a model for immune-mediated bone marrow failure (aplastic anemia mouse model). Mice with aplastic anemia were treated with cyclosporin A monotherapy, cyclosporin A in combination with stanozolol, and cyclosporin A in combination with danazol for 30 days. Peripheral blood cell counts once a week and bone marrow colony assays at the end of 1 month were performed. The proportion of T cell subsets, level of inflammatory factors, erythropoietin, and thrombopoietin were detected before and after treatment. The levels of erythropoietin receptors on bone marrow mononuclear cells after treatment were tested using western blotting.Results: In the ex vivo experiments, the number of burst-forming units-erythroid; colony-forming units-granulocyte and macrophage; and colony-forming units-granulocyte, erythrocyte, monocyte, and megakaryocyte in the patients with aplastic anemia were significantly lower than that in the normal controls (P < 0.05). However, the number of colonies and mean fluorescence intensity of CD235a or CD41 expression in the harvested cultured cells were not significantly different among the different treatment groups in the patients with aplastic anemia, normal controls, and K562 cell lines. These results show that stanozolol and danazol produce no direct hematopoiesis-stimulating effects on progenitor cells. In the in vivo experiment, the mice with aplastic anemia treated with cyclosporin A and danazol exhibited the most rapid recovery of platelet; the platelet count returned to normal levels after 3 weeks of treatment, which was at least 1 week earlier than in the other groups. In contrast, mice treated with cyclosporin A and stanozolol exhibited the highest hemoglobin level at the end of treatment (P < 0.05). Bone marrow colony assays at 30 days showed that the number of burst-forming units-erythroid was the highest in mice treated with cyclosporin A and stanozolol, while the number of colony-forming units-granulocyte and macrophage was the highest in those treated with cyclosporin A and danazol. Compared to cyclosporin A monotherapy, additional stanozolol and danazol can both increase the level of regulatory T cells and upregulate interleukin-10, inhibiting the expression of tumor necrosis factor-α (P < 0.05). However, IL-2 was more effectively reduced by danazol than by stanozolol (P < 0.05). The cyclosporin A- and stanozolol-treated mice showed higher serum erythropoietin (corrected by hemoglobin level) and higher erythropoietin receptor levels in bone marrow mononuclear cells than the other groups (P < 0.05).Conclusions: Neither stanozolol nor danazol directly stimulated hematopoiesis in vitro. However, in vivo, stanozolol may exhibit an advantage in improving erythropoiesis, while danazol may induce stronger effects on platelets. Both danazol and stanozolol exhibited immunosuppressive roles. Stanozolol could enhance the secretion of erythropoietin and expression of erythropoietin receptor in bone marrow mononuclear cells.

Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

ABSTRACTThe Prp8 intein is one of the most widespread eukaryotic inteins, present in important pathogenic fungi, including Cryptococcus and Aspergillus species. Because the processed Prp8 carries out essential and non-redundant cellular functions, a Prp8 intein inhibitor is a mechanistically novel antifungal agent. In this report, we demonstrated that cisplatin, an FDA-approved cancer drug, significantly arrested growth of Prp8 intein-containing fungi C. neoformans and C. gattii, but only poorly inhibited growth of intein-free Candida species. These results suggest that cisplatin arrests fungal growth through specific inhibition of the Prp8 intein. Cisplatin was also found to significantly inhibit growth of C. neoformans in a mouse model. Our results further showed that cisplatin inhibited Prp8 intein splicing in vitro in a dose-dependent manner by direct binding to the Prp8 intein. Crystal structures of the apo- and cisplatin-bound Prp8 inteins revealed that two degenerate cisplatin molecules bind at the intein active site. Mutation of the splicing-site residues led to loss of cisplatin binding, as well as impairment of intein splicing. Finally, we found that overexpression of the Prp8 intein in cryptococcal species conferred cisplatin resistance. Overall, these results indicate that the Prp8 intein is a novel antifungal target worth further investigation.

In recent years, many scholars have been committed to improving the security and practicability of chaotic image encryption. In addition, their proposed schemes mainly focus on two aspects, new or improved chaotic systems and new or improved encryption processes. However, according to cryptanalysis works of scholars, encryption processes of chaotic image encryption schemes deserve more attentions. In this paper, a recently reported chaotic image encryption scheme named the 2D logistic-adjusted-sine-map-based image encryption scheme is comprehensively investigated, and some security, practicability, and rationality problems are found. Therefore, we first point out these problems existing in the reported encryption scheme and make some improvements in practicability and rationality. Next, under the conditions of chosen plaintext attack, we cryptanalyze it and propose a corresponding attack algorithm. For our attack algorithm, simulation test results show that it can completely recover plain images without knowing any secret key related information. Finally, we also present some possible improvements for the security problems of chaotic image encryption scheme under study.

According to the research works of the literatures on chaotic cryptanalysis, many recent chaotic image encryption algorithms cannot resist chosen-plaintext attack. Although some chaotic image encryption algorithms introduce plain-image information, they still violate some design requirements of modern cryptosystems. Therefore, after analyzing many literatures related to chaotic image encryption, we propose a plain-image-related chaotic image encryption algorithm based on the deoxyribonucleic acid (DNA) sequence operation and discrete logarithm. As we know, the discrete logarithm calculation is a complex non-linear calculation, introducing it can increase the complexity of the encryption process. More importantly, discrete logarithm values are significantly different under different generators, and the multiplicative group adopted in the proposed algorithm has as many as 128 generators. Therefore, by using two generators determined by the secret key and the hash value of the plain-image respectively, we not only expand the key space, but also greatly improve the plain-image sensitivity and plain-image relevancy of the encryption process. In addition, the proposed algorithm improves the way of using the hash value of the plain-image. In this way, once the secret key is selected, chaotic sequences can be generated in advance and reused to improve the encryption efficiency. Similarly, the proposed algorithm also introduces the DNA sequence operation with high parallelism to further improves the encryption efficiency. Simulation tests and comparative analyses show that the proposed algorithm can not only resist common attacks, but also outperform some recent chaotic image encryption algorithms in many aspects.

Robust chaos in the discrete system is suggested to have practical as well as theoretical importance since it can obtain reliable operation in the chaotic mode. However, it receives only moderate attention and only focuses on a finite chaotic parameter space and small Lyapunov exponents. This paper introduces a two-dimensional smooth map and studies its robustness of chaos in the infinite parameter space. Then, a compound operation-based optimization control method is introduced to increase the map complexity in the measure of Lyapunov exponent. The introduced method is simple and provides a new pathway for exploring the robustness and complexity of discrete chaotic system. Finally, we design a chaos-based pseudo-random number generator (CPNG) based on the optimized robust chaotic map, and the careful analysis shows that the proposed CPNG has high quality of randomness and has passed the rigorous National Institute of Standards and Technology (NIST) test.

Abstract Background The allocation of health resources in primary health care institutions (PHCI) is crucial to health reform. China has recently implemented many reform measures emphasizing the provision of primary health care services, with equity as one of the major goals. The aim of this study was to analyze the quantity, quality, and distribution of health resources in Liaoning Province from 2005 to 2017. Methods Data were drawn from the annual financial report from 2005 to 2017 and information from the Liaoning Province Department of Statistics. Numbers of beds and physicians were used as indicators of health resources. Capital assets per bed, value of medical equipment per bed, operational space per bed, and number of physicians with different educational levels were used as indicators of quality of health resources. Concentration indices (CI) and Gini coefficients were calculated. Results There was a steady rise in health resources in PHCI. From 2005 to 2017, the quality of health resources improved. The CI of beds showed an overall downward trend, indicating an improvement in the disparity among PHCI. There was a similar trend in the CI of fixed assets per bed. The Gini coefficients of physicians overall and physicians with different educational levels were almost always

Inteins can act as post-translational environmental sensors in vivo. Here the authors characterize two inteins present in the Mycobacterium smegmatis replicative helicase DnaB that display distinct splicing behaviors and are differentially sensitive to inhibition by biological stressors and propose that splicing inhibition could modulate DnaB levels to protect the cell against replication stress.

Flaviviruses cause a significant amount of mortality and morbidity, especially in regions where they are endemic. A recent example is the outbreak of Zika virus throughout the world. Development of antiviral drugs against different viral targets is as important as the development of vaccines. During viral replication, a single polyprotein precursor (PP) is produced and further cleaved into individual proteins by a viral NS2B-NS3 protease complex together with host proteases. Flavivirus protease is one of the most attractive targets for development of therapeutic antivirals because it is essential for viral PP processing, leading to active viral proteins. In this review, we have summarized recent development in drug discovery targeting the NS2B-NS3 protease of flaviviruses, especially Zika, dengue, and West Nile viruses.