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Worldwide antibiotic abuse accelerates the evolution of drug-resistant super bacteria, which goes against the war toward bacterial infection. Antibiotic-loaded nanoparticles as a typical form of nanomedicine hold great promise in combating bacterial infection, which requires the development of a suitable carrier. Tannic acid (TA) showed an inhibition effect on both Gram-positive and -negative strains; however, there are no reports on the development of antibacterial nanoformulations based on TA itself. We could get PTA NPs using a one-pot method, and their size and ζ-potential were characterized. Herein, we carefully tuned the polymerization of TA to give well-dispersed polytannic acid nanoparticles (PTA NPs) with a size of 100 nm. Moreover, our results demonstrated that PTA NPs showed enhanced antibacterial effects on both Gram-positive and -negative strains as compared to free TA. Especially, PTA NPs can preferably accelerate the healing ofiStaphylococcus/i-infected wounds. Based on its structure, we suggested that PTA NPs may have a similar property to polydopamine nanoparticles to offer high drug loading for potential combination therapy for extended application in bacterial infection management.

Infection-induced chronic wounds cause prolonged pains, a high risk of amputation, and even increased mortality in immunocompromised patients. Here we report an antibacterial microneedle (MN) patch, which features high degradability in biological fluids and gelatinase-responsive release of an antibacterial photothermal peptide AMP-Cypate. We first synthesize gelatin nanoparticles (GNPs) and then conjugate the AMP-Cypate to afford composite AMP-Cypate@GNPs. The proteinaceous nanoparticles can responsively release AMP-Cypate in the presence of gelatinase, an enzyme secreted specifically by Staphylococcus aureus (S. aureus). AMP-Cypate@GNPs were then deposited in the tips of MNs fabricated by PVP and recombinant human type III collagen (Col III) to devise the antibacterial MN/AMP-Cypate@GNP patches. When applied to the infection site, MNs break through the epidermis and the stratum corneum, dissolve in the infected dermis, reach the bacterial colony or biofilm, release AMP-Cypate@GNPs, and exert a gelatinase-responsive photothermal therapy under near-infrared (NIR) irradiation to kill the pathogen S. aureus. In a rat model of staphylococcal infection-induced chronic wounds mimicking the condition of diabetic foot ulcer, the antibacterial MN/AMP-Cypate@GNP patches eradiated the bacterial infection and resulted in complete healing of the wounds, proving its potential application in the treatment of chronic wound infections and diabetic foot ulcers.

Traditional onefold data-driven methods for fault detection in complex process industrial systems with high-dimensional, linear, nonlinear, Gaussian, and non-Gaussian coexistence often have less than satisfactory monitoring performance because only a single distribution of process variables is considered. To address this problem, a hybrid fault detection model based on PCA-KPCA-ICA-KICA-BI (Bayesian inference) is proposed, taking into account the advantages of principal component analysis (PCA), kernel principal component analysis (KPCA), independent component analysis (ICA), and kernel independent component analysis (KICA) in terms of dimensionality reduction and feature extraction. Foremost, this paper proposed a nonlinear evaluation method and divided the feature variables into Gaussian linear blocks, Gaussian nonlinear blocks, non-Gaussian linear blocks, and non-Gaussian nonlinear blocks by using the Jarque–Bera (JB) test and nonlinear discrimination method. Each division was monitored by the PCA-KPCA-ICA-KICA model, and finally the Bayesian fusion strategy proposed in this study is used to synthesize the detection results for each block. The hybrid model helps in evaluating variable features and bettering detection performance. Ultimately, the superiority of this hybrid model was verified through the Tennessee Eastman (TE) process and the Continuous Stirred Tank Reactor (CSTR) process, and the fault monitoring results showed an average accuracy of 85.91% for this hybrid model.

Background: Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations. Objective: This study focused on the preparation of stable nicotine-encapsulated ethosomes. Methods: During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy. Results: When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13±1.40), smallest particle size (106.0±11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotine-encapsulated ethosomes (ethanol: PG=5:5, w/w) were an efficient and stable transdermal delivery system. Conclusion: The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.

Traffic accidents have become one of the biggest public health safety matters, which has raised many concerns from citizens and city managers. Accurate traffic accident prediction can not only assist the government in making decisions in advance but also enhance public trust in public safety. Conventional spatio-temporal prediction models, limited by the skewed distributions and sparse labels of traffic accident occurrence, are prone to overfitting. Inspired by hypergraph learning and self-supervised learning, this paper suggests a sparse spatio-temporal dynamic hypergraph learning (SST-DHL) framework to capture the higher-order dependencies in sparse traffic accidents. Specifically, a multi-view spatio-temporal convolution block is employed first to capture the local spatio-temporal correlation and inherent semantics of traffic accidents. Then we propose a cross-regional dynamic hypergraph learning model to capture global spatio-temporal dependencies beneath the entire urban landscape. In addition, a two-supervised self-learning paradigm is intended to strengthen the representation of sparse traffic occurrences by regional self-identification, which can capture local and global spatio-temporal traffic patterns. The proposed model is applicable to most sparse datasets for traffic forecasts. Extensive experiments was conducted on two heterogeneous accident datasets from New York City and London, and the results shows an average improvements of 7.21%-23.09% at different sparsity levels compared to the optimal baselines. More importantly, the proposed SST-DHL improves the interpretability of model results, which demonstrates that hypergraph learning can efficiently capture the complex higher-order spatio-temporal dependencies among different traffic accident instances.

This study used capillary electrophoresis with fluorescence detection- and a partial-filling mode-based method for chiral separation of ofloxacin. The deoxyribonucleic acid oligonucleotides with different base sequences were studied as potential chiral selectors including deoxyribonucleic acid tetrahedron, G-quadruplex, and G-riched double-strand deoxyribonucleic acid. Under the optimized conditions, all the deoxyribonucleic acid chiral selectors exhibited excellent chiral separation capabilities with a resolution higher than 1.5. The electrophoretic behavior of the ofloxacin enantiomer might result from the intermediate conjugate with different stabilities between chiral selectors and analytes by a combination of the hydrogen bond and spatial recognition structure. Moreover, satisfactory repeatability regarding run-to-run and interday repeatability was obtained, and all the relative standard deviation values of migration times and resolutions were below 4% (n = 6). Conclusively, both spatial structure and arrangement of the G bases potentiated the chiral separation capability of deoxyribonucleic acid for ofloxacin enantiomer. This work offered a stepping stone for enantioseparation using deoxyribonucleic acid as chiral selectors.

The continued evolution and emergence of novel influenza viruses in wild and domestic animals poses an increasing public health risk. Two human cases of H3N8 avian influenza virus infection in China in 2022 have caused public concern regarding the risk of transmission between birds and humans. However, the prevalence of H3N8 avian influenza viruses in their natural reservoirs and their biological characteristics are largely unknown. To elucidate the potential threat of H3N8 viruses, we analyzed five years of surveillance data obtained from an important wetland region in eastern China and evaluated the evolutionary and biological characteristics of 21 H3N8 viruses isolated from 15,899 migratory bird samples between 2017 and 2021. Genetic and phylogenetic analyses showed that the H3N8 viruses circulating in migratory birds and ducks have evolved into different branches and have undergone complicated reassortment with viruses in waterfowl. The 21 viruses belonged to 12 genotypes, and some strains induced body weight loss and pneumonia in mice. All the tested H3N8 viruses preferentially bind to avian-type receptors, although they have acquired the ability to bind human-type receptors. Infection studies in ducks, chickens and pigeons demonstrated that the currently circulating H3N8 viruses in migratory birds have a high possibility of infecting domestic waterfowl and a low possibility of infecting chickens and pigeons. Our findings imply that circulating H3N8 viruses in migratory birds continue to evolve and pose a high infection risk in domestic ducks. These results further emphasize the importance of avian influenza surveillance at the wild bird and poultry interface.

The H10 subtypes of avian influenza viruses pose a continual threat to the poultry industry and human health. The sporadic spillover of H10 subtypes viruses from poultry to humans is represented by the H10N8 human cases in 2013 and the recent H10N3 human infection in 2021. However, the genesis and characteristics of the recent reassortment H10N3 viruses have not been systemically investigated. In this study, we characterized twenty H10N3 viruses isolated in live poultry markets during routine nationwide surveillance in China from 2014 to 2021. The viruses in the recent reassortant genotype acquired their hemagglutinin (HA) and neuraminidase (NA) genes from the duck H10 viruses and H7N3 viruses, respectively, whereas the internal genes were derived from chicken H9N2 viruses as early as 2019. Receptor-binding analysis indicated that two of the tested H10N3 viruses had a higher affinity for human-type receptors than for avian-type receptors, highlighting the potential risk of avian-to-human transmission. Animal studies showed that only viruses belonging to the recent reassortant genotype were pathogenic in mice; two tested viruses transmitted via direct contact and one virus transmitted by respiratory droplets in guinea pigs, though with limited efficiency. These findings emphasize the need for enhanced surveillance of H10N3 viruses. This article is protected by copyright. All rights reserved.

Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K’s indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

Bacterial infection of wounds delays the healing process, increases the risk of chronic trauma associated with pain and complications, and offers a breeding ground for drug-resistant bacteria. A rapid and effective eradication of the bacterial species in the wound area is thus important. Herein, we designed a phototherapeutic antibacterial platform based on peptides and copper sulfide nanodots (CuS NDs) for multi-mechanistic eradication of bacteria colonized on the wound surface. The antimicrobial peptide weaves into a network in the form of a hydrogel, which supports CuS NDs to generate heat and produce reactive oxygen species (ROS) under the irradiation of near-infrared light (NIR). The heat and ROS generated

Ependymomas arise from ependymal cells lining the ventricles and central canal of the spinal cord and can occur throughout the whole neuraxis. The lesion rarely occurs in extracranial or extraspinal regions, particularly in the uterine broad ligament. Thus, for the pathogenesis of nonsacral extra-central nervous system (CNS) ependymomas remains elusive. Here, we describe a rare case of primary uterine broad ligament. ependymoma with cell-cycle-checkpoint kinase 2 (CHEK2) p.H371Y germline mutation. A 45-year-old woman presented with a uterine mass. The transvaginal sonographic examination confirmed a 4.4 cm × 3.7 cm, cystic and solid, mass located on the right side uterine wall near isthmus. First, laparoscopy with the neoplasm resection was carried out. Based on morphological and immunohistochemical characteristics of tumor cells that expressed glial fibrillary acidic protein (GFAP), S-100, and vimentin, the tumor was diagnosed as an ependymoma. After that, she underwent a laparotomic total hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. Furthermore, we performed next-generation sequencing (NGS) of the patient's resected tumor tissue and peripheral blood and identified a novel CHEK2 p.H371Y germline mutation. Following surgery, the patient received oral tamoxifen (10 mg 2/day) and followed by letrozole (2.5 mg/day) for 6 months. The patient remained disease-free after 4 years of follow-up. Conceivably, CHEK2 p.H371Y is a driving gene for the development of extra-CNS ependymoma.

H16 avian influenza viruses mainly circulate in wild migratory gulls worldwide, and the infection risks in poultry and mammals remain largely unknown. In this study, we isolated a novel H16N3 virus from migratory gulls in eastern China in 2021. Genetic analysis indicated that the H16N3 virus originated from the H16 and H13 viruses that circulated in wild birds. This H16N3 virus has not adapted to replicate in chickens, ducks, or mice, although it can be transmitted between inoculated and contacted birds. The circulation of H16Nx viruses in the Northern Hemisphere indicates that we should strengthen active surveillance to monitor their prevalence and evolution in migratory gulls and their introduction into other migratory and domestic waterfowl.

Avian influenza viruses continue to present challenges to animal and human health. Viruses bearing the hemagglutinin (HA) gene of the H5 subtype and H7 subtype have caused 2634 human cases around the world, including more than 1000 deaths. These viruses have caused numerous disease outbreaks in wild birds and domestic poultry, and are responsible for the loss of at least 422 million domestic birds since 2005. The H5 influenza viruses are spread by migratory wild birds and have caused three waves of influenza outbreaks across multiple continents, and the third wave that started in 2020 is ongoing. Many countries in Europe and North America control highly pathogenic avian influenza by culling alone, whereas some countries, including China, have adopted a "cull plus vaccination" strategy. As the largest poultry-producing country in the world, China lost relatively few poultry during the three waves of global H5 avian influenza outbreaks, and nearly eliminated the pervasive H7N9 viruses that emerged in 2013. In this review, we briefly summarize the damages the H5 and H7 influenza viruses have caused to the global poultry industry and public health, analyze the origin, evolution, and spread of the H5 viruses that caused the waves, and discuss how and why the vaccination strategy in China has been a success. Given that the H5N1 viruses are widely circulating in wild birds and causing problems in domestic poultry around the world, we recommend that any unnecessary obstacles to vaccination strategies should be removed immediately and forever.

Oxidative stress initiated by reactive oxygen species (ROS) is the cause of many acquired or congenital skin diseases. Oral antioxidants or using topical antioxidants preparations may bring the nonspecific distribution of drugs or anaphylaxis due to repeated use. In this study, a biocompatible gene vector by cross-linking of chitosan-oligosaccharide (CSO) and N,N’-cystamine-bis-acrylamide (CBA) was synthesized (CSO-CBA), which could carry therapeutic genes into the skin, express functional proteins in epidermal cells, and play an efficient antioxidant effect. Infrared and 1H NMR spectrum data showed that CSO-CBA was successfully synthesized. Gel electrophoresis results showed that the gene could be successfully compressed by the carrier and can be released in a reducing environment. Hemolysis experiments showed that the carrier had good biocompatibility. Transdermal gene delivery experiments proved that the vector can bring genes into the skin, express functional proteins, and protect the skin from reactive oxygen species damage after 7 days of administration. Skin compatibility experiments show that our therapy is biocompatible. Our study provides a minimally invasive and painless, high-biocompatibility, and long-term effective treatment for skin damage caused by reactive oxygen species, which has a potential application.

Currently, nucleic acid preparations have gained much attention due to their unique working principle and application value. However, as macromolecular drugs, nucleic acid preparations have complex construction and poor stability. The current methods to promote stability face problems such as high cost and inconvenient operatios. In this study, the hydrophilic pharmaceutical excipient PEG was used to gelate nucleic acid preparations to avoid the random movements of liquid particles. The results showed that PEG gelation significantly improved the stability of PEI25K−based and liposome−based nucleic acid preparations, compared with nucleic acid preparations without PEG gelation. After being stored at 4 °C for 3 days, non−PEG gelled nucleic acid preparations almost lost transfection activity, while PEGylated preparations still maintained high transfection efficiency. Fluorescence experiments showed that this effect was caused by inhibiting particle aggregation. The method described in this study was simple and effective, and the materials used had good biocompatibility. It is believed that this study will contribute to the better development of gene therapy drugs.

H6 avian influenza virus (AIV) is one of the most prevalent AIV subtypes in the world. Our previous studies have demonstrated that H6 AIVs isolated from live poultry markets pose a potential threat to human health. In recent years, increasing number of H6 AIVs has been constantly isolated from poultry farms. In order to understand the biological characteristics of H6 AIVs in the context of farms, here, we analyzed the phylogenetic relationships, antigenicity, replication in mice and receptor binding properties of H6 AIVs isolated from farms in China between 2014 and 2018. Phylogenetic analysis showed that 19 different genotypes were formed among 20 representative H6 viruses. Notably, the internal genes of these H6 viruses exhibited complicated relationships with different subtypes of AIVs worldwide, indicating that these viruses are the products of complex and frequent reassortment events. Antigenic analysis revealed that 13 viruses tested were divided into 3 antigenic groups. 10 viruses examined could all replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that some of the H6 AIVs bound to both α-2, 3-linked glycans (avian-type receptor) and α-2, 6-linked glycans (human-type receptor), thereby posing potential threat to human health. Together, these findings revealed the prevalence, complicated genetic evolution, diverse antigenicity, and dual receptor binding specificity of H6 AIVs in the settings of poultry farms, which emphasize the importance to continuously monitor the evolution and biological properties of H6 AIVs in nature. This article is protected by copyright. All rights reserved.

Background Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Methods LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan–Meier analyses were applied to assess different therapy modalities. Results A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60–79 (OR 0.57; 95% CI 0.41–0.78; p p p Conclusions LCC patients with age

BackgroundAntimicrobial resistance to metronidazole has emerged after several decades of worldwide use of the drug. The purpose of this study was to evaluate the effectiveness, safety and population pharmacokinetics of morinidazole plus levofloxacin in adult women with pelvic inflammatory disease (PID).MethodsPatients in 30 hospitals received a 14-day course of 500 mg intravenous morinidazole twice daily plus 500 mg of levofloxacin daily. A total of 474 patients were included in the safety analysis set (SS); 398 patients were included in the full analysis set (FAS); 377 patients were included in the per protocol set (PPS); 16 patients were included in the microbiologically valid (MBV) population.ResultsThe clinical resolution rates in the FAS and PPS populations at the test of cure (TOC, primary effectiveness end point, 7–30 days post-therapy) visit were 81.91 and 82.49% (311/377), respectively. There were 332 patients who did not receive antibiotics before treatment, and the clinical cure rate was 82.83%. Among 66 patients who received antibiotics before treatment, 51 patients were clinically cured 7–30 days after treatment, with a clinical cure rate of 77.27%. The bacteriological success rate in the MBV population at the TOC visit was 87.5%. The minimum inhibitory concentration (MIC) values of morinidazole for use against these anaerobes ranged from 1 to 8 μg/mL. The rate of drug-related adverse events (AEs) was 27.43%, and no serious AEs or deaths occurred during the study.ConclusionsThe study showed that treatment with a 14-day course of intravenous morinidazole, 500 mg twice daily, plus levofloxacin 500 mg daily, was effective and safe. The results of this study were consistent with the results of a phase III clinical trial, which verified the effectiveness and safety of morinidazole.

According to the characteristics of the flow in the corrugated pipe, Fluent is used to simulate the 3D numerical simulation of the fluid in the corrugated pipe and the ordinary straight pipe by using the RNG k-ε model. Water at a certain temperature is used as the medium. The flow velocity is 0.5 m/s, 0.75 m/s, 1 m/s, 1.25 m/s, 1.5 m/s, in-pipe characteristics with a pipe diameter of 25mm and a pipe length of 1030mm. The simulation adopts the unstructured hexahedral mesh in the simulation, and the SIMPLE algorithm is used for pressure correction; the algebraic equation is iteratively solved by the over-relaxation method. The temperature and velocity at different cross-sections when the flow and heat exchange enter the fully developed stage are obtained through simulation calculation, and they are compared with the related characteristics of flow and heat transfer in the light pipe. The cooling tower of the straight pipe is tested, and the results show that the heat transfer performance of the corrugated pipe is better than that of the ordinary straight pipe.

The traditional water cooling system of electric drive compressor in natural gas long distance pipeline uses cooling water tower, which has many problems in practical engineering: spraying water for cooling consumes a large amount of water continuously, continuous dosing and sewage discharge is needed, and winter anti-freezing measures are complex and so on. In view of the above defects of cooling water tower, this paper introduces a new type of composite water cooling system, which is completely closed, cooling without spraying water, no water consumption and discharge, daily maintenance free, its comprehensive advantages are obvious. The first composite water cooling system has been put into operation for more than 5 years, with good functions and performance, and has been widely used in electric drive compressor engineering stations.

Background: Promising cancer chemotherapy requires the development of suitable drug delivery systems (DDSs). Previous research has indicated that a hydrogel is a powerful DDS for tumor therapy and holds great potential to offer a feasible method for cancer management. Methods: In this study, glutathione-gellan gum conjugate (GSH-GG) was synthesized through chemical reaction. Doxorubicin hydrochloride (DOX) was loaded into GSH-GG to accomplish DOX-loaded GSH-GG. The properties, injectability, drug release, and in vitro and in vivo anticancer effects of DOX-loaded GSH-GG were tested. Results: DOX-loaded GSH-GG showed a temperature-ion dual responsive gelling property with good viscosity, strength, and injectability at an optimized gel concentration of 1.5%. In addition, lower drug release was found under acidic conditions, offering beneficial long-acting drug release in the tumor microenvironment. DOX-loaded GSH-GG presented selective action by exerting substantially higher cytotoxicity on cancer cells (4T1) than on normal epithelial cells (L929), signifying the potential of complete inhibition of tumor progression, without affecting the health quality of the subjects. Conclusions: GSH-GG can be applied as a responsive gelling material for delivering DOX for promising cancer therapy.

H5N1 avian influenza viruses bearing the clade 2.3.4.4b hemagglutinin gene have been widely circulating in wild birds and are responsible for the loss of over 70 million domestic poultry in Europe, Africa, Asia, and North America since October 2020. During our routine surveillance, 13 H5N1 viruses were isolated from 26,767 wild bird and poultry samples that were collected between September 2021 and March 2022 in China. To investigate the origin of these Chinese isolates and understand their genetic relationship with the globally circulating H5N1 viruses, we performed a detailed phylogenic analysis of 233 representative H5N1 strains that were isolated from 28 countries. We found that, after they emerged in the Netherlands, the H5N1 viruses encountered complicated gene exchange with different viruses circulating in wild birds and formed 16 genotypes. Genotype one (G1) was predominant, being detected in 22 countries, whereas all other genotypes were only detected in one or two continents. H5N1 viruses of four genotypes (G1, G7, G9, and G10) were detected in China; three of these genotypes have been previously reported in other countries. The H5N1 viruses detected in China replicated in mice, with pathogenicity varying among strains; the G1 virus was highly lethal in mice. Moreover, we found that these viruses were antigenically similar to and well matched with the H5-Re14 vaccine strain currently used in China. Our study reveals the overall picture of H5N1 virus evolution and provides insights for the control of these viruses.

BackgroundA systematic analysis of prognostic factors concerning endometrial clear cell carcinoma (ECCC) is lacking. The current study aimed to construct nomograms predicting the overall survival (OS) of ECCC patients.MethodsWe performed a retrospective study, and predicted nomograms for 3-, 5-, and 10-year OS were established. The nomograms were verified with the consistency index (C-index), calibration curve, and decision curve analysis (DCA).ResultsA total of 1778 ECCC patients, 991 from FIGO stage I/II and 787 from FIGO stage III/IV, were included in this study. The age at diagnosis, marital status, T stage, tumor size, and surgery-independent prognostic factors in FIGO stage I/II, and the age at diagnosis, T stage, lymph node involvement, distant metastasis, tumor size, surgery, radiotherapy, and chemotherapy in FIGO stage III/IV were independent prognostic factors. The C-indexes of the training and validation group were 0.766 and 0.697 for FIGO stage I/II and 0.721 and 0.708 for FIGO stage III/IV, respectively. The calibration curve revealed good agreement between nomogram-predicted and actual observation values. The DCA established that nomograms had better clinical benefits than the traditional FIGO stage.ConclusionsThe predicted nomograms showed good accuracy, excellent discrimination ability, and clinical benefits, depicting their usage in clinical practice.

Background: Current studies still have a controversy on the effect and doses of irradiation (IR) on bone regeneration. Moreover, the mechanisms of IR to bone regeneration mainly focus on the direct effects on osteoblasts, with neglect to the role of the surrounding immune environment. Our purpose was to explore the effect of IR on osteoblasts proliferation and macrophages polarity.Results: Here in this study, we firstly established the rat cranial defects model and revealed that low-dose IR≤2 Gy gradually promoted bone regeneration, while high-dose IR>2Gy inhibited bone regeneration. The change of macrophage polarity in peripheral blood samples showed that low-dose IR≤2 Gy triggered M2 polarization of macrophages, high-dose IR>2 Gy led to M1 polarization. The cellular level also showed the similar results, mouse leukemia cells of monocyte macrophages cells (Raw264.7) exhibited M2 polarization under low-dose IR≤2 Gy, and M1 polarization under high-dose IR>2Gy. Furthermore low-dose IR≤2 Gy promoted the proliferation of osteoblasts, while high-dose IR>2 Gy exhibited the opposite result. The co-culture results showed that low-dose IR≤2 Gy not only promoted bone regeneration through osteoblasts proliferation, but also promoted bone regeneration through M2 polarization of Raw264.7 cells, while high-dose IR>2 Gy had the opposite effect.Conclusions: Our findings have revealed that low-dose IR≤2 Gy promotes bone regeneration by indirectly promoting macrophage M2 polarization and direct osteoblast proliferation, while high-dose IR>2 Gy has the opposite effect, which might offer inspirations for the related studies.

To prevent the gas over limit in the upper corner of the 215101 working face of the Yue Nan coal mine, a numerical simulation method was used to analyze the gas concentration in the upper corner of the working face at different air intake volumes and mining velocities. The research results show that the gas concentration in the upper corner is 0.78, 0.52, 0.39, and 0.32% when the wind speed of the intake airflow roadway is 1, 1.5, 2, and 2.5 m/s, respectively, and an optimal wind speed of the intake airflow roadway is selected as 2 m/s. When the wind speed of the intake airflow roadway is 2 m/s, the working face mining velocity is 1, 2, 3, and 4 m/d, and the gas concentration in the upper corner is 0.27, 0.39, 0.58, and 0.83%, respectively, and an optimal working face mining velocity of 3 m/d is selected. Under the optimal mining conditions, the working face wind leakage area is divided, with 0∼30 m of the working face as the main leakage area and 150-180 m as the wind flow compensation area. According to the wind speed in the gob, the wind flow disturbance area is divided, the gob 0-50 m is the wind flow intense disturbance area, which is the main area of the upper corner gas source; the gob 50-62 m is the wind flow medium disturbance area, which is the secondary area of the upper corner gas source; the gob 62-75 m is the slight disturbance area, which has less influence on the upper corner gas concentration; the gob after 75 m is the wind flow undisturbed area, and the upper corner gas concentration is almost unaffected by it.

ObjectiveThe study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.MethodsThe top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.ResultsThe average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).ConclusionsThe United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.

Intranasal administration, which can bypass the blood–brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.

H10Nx influenza viruses have caused increasing public concern due to their occasional infection of humans. However, the genesis and biological characteristics of H10 viruses in migratory wild birds are largely unknown. In this study, we conducted active surveillance to monitor circulation of avian influenza viruses in eastern China and isolated five H10N4 and two H10N8 viruses from migratory birds in 2020. Genetic analysis indicated that the hemagglutinin (HA) genes of the seven H10 viruses were clustered into the North American lineage and established as a novel Eurasian branch in wild birds in South Korea, Bangladesh, and China. The neuraminidase (NA) genes of the H10N4 and H10N8 viruses originated from the circulating HxN4 and H5N8 viruses in migratory birds in Eurasia. We further revealed that some of the novel H10N4 and H10N8 viruses acquired the ability to bind human-like receptors. Animal studies indicated that these H10 viruses can replicate in mice, chickens, and ducks. Importantly, we found that the H10N4 and H10N8 viruses can transmit efficiently among chickens and ducks but induce lower HA inhibition (HI) antibody titers in ducks. These findings emphasized that annual surveillance in migratory waterfowl should be strengthened to monitor the introduction of wild-bird H10N4 and H10N8 reassortants into poultry.

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.

The globally circulating H5N8 avian influenza viruses bearing the clade 2.3.4.4b hemagglutinin (HA) gene are responsible for the loss of more than 33 million domestic poultry since January 2020. Moreover, the H5N8 viruses have reassorted with other avian influenza viruses and formed H5N1, H5N2, H5N3, H5N4, and H5N5 viruses in Europe, Africa, and North America. In this study, we analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans, and found these viruses formed seven different genotypes by deriving the clade 2.3.4.4b HA gene of H5N8 viruses, the neuraminidase of domestic duck H5N6 viruses, and internal genes of different viruses that previously circulated in domestic ducks and wild birds in China. Two of these genotypes (genotype 3 and genotype 6) have caused human infections in multiple provinces. The H5N6 viruses isolated from poultry have distinct pathotypes in mice; some of them replicate systemically and are highly lethal in mice. Although these viruses exclusively bind to avian-type receptors, it is worrisome that they may obtain key mutations that would increase their affinity for human-type receptors during replication in humans. Our study indicates that the novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 viruses were generated through reassortment in domestic ducks and may have spread across a wide area of China, thereby posing a new challenge to the poultry industry and human health. Our findings emphasize the importance of careful monitoring, evaluation, and control of the H5N6 viruses circulating in nature.

Damage or injury to the skin creates wounds that are vulnerable to bacterial infection, which in turn retards the process of skin regeneration and wound healing. In patients with severe burns and those with chronic diseases, such as diabetes, skin infection by multidrug-resistant bacteria can be lethal. Therefore, a broad-spectrum therapy to effectively eradicate bacterial infection through a mechanism different from that of antibiotics is much sought after. We successfully synthesized antibacterial photodynamic gold nanoparticles (AP-AuNPs), which are self-assembled nanocomposites of an antibacterial photodynamic peptide and poly(ethylene glycol) (PEG)-stabilized AuNPs. The AP-AuNPs exhibited aqueous and light stability, a satisfactory generation of reactive oxygen species (ROS), and a remarkable antibacterial effect toward both Gram-positive

A novel peptide containing antimicrobial sequence and gelatinase cleavage sites was designed for Staphylococcus aureus detection. Since Staphylococcus aureus could secrete gelatinase, the fluorescein labeled peptide GKRWWKWWRRPLGVRGC could be recognized and cleaved. The obtained products were able to be analyzed by capillary electrophoresis with fluorescence detection. To explore the effect of Staphylococcus aureus concentration on enzyme digestion ability of peptide, Staphylococcus aureus with different concentrations were incubated with the peptide. Results indicated that capillary electrophoretic method was efficient for determining Staphylococcus aureus content. Compared with traditional approaches for Staphylococcus aureus detection, capillary electrophoresis possessed higher efficiency, enhanced sensitivity, and low sample consumption. Moreover, the proposed peptide also presented desirable antimicrobial activity. It suggested that the novel antimicrobial peptide used in this research opens a new path of detecting Staphylococcus aureus by capillary electrophoretic method.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS) are likely to receive programmed cell death 1 (PD-1) inhibitors, despite limited evidence. The aim of the present study was to report the clinical outcomes and potential prognostic biomarkers in advanced NSCLC patients with poor PS receiving PD-1 inhibitors. METHODS: We conducted a retrospective study enrolling 101 advanced NSCLC patients from our hospital. Data of patients with poor PS 2–4 receiving PD-1 inhibitors were retrieved from medical records. Patients were stratified based on dichotomized baseline neutrophil-to-lymphocyte ratio (NLR), change in NLR (ΔNLR; 6 weeks post-treatment NLR minus baseline NLR), and their combination. The receiver-operating characteristic curve was used to assess the best cutoff for NLR. Multivariate Cox analysis was used to evaluate the prognostic value of NLR and ΔNLR for patients’ survival. RESULTS: The optimal cutoff for NLR was 4.5. The median follow-up was 25.7 months, baseline NLR ≥4.5, and ΔNLR ≥0, which were independently and significantly associated with shorter overall survival (both P=0.002) and progression-free survival (P=0.004 for NLR and P

DNA possesses various chemical and physical properties which make it important in biological analysis. The opportunity for DNA to 'meet' capillary-based microsystems is rapidly increasing owing to the expanding development of miniaturization. Novel capillary-based methods can provide favourable platforms for DNA-ligand interaction assay, DNA translocation study, DNA separation, DNA aptamer selection, DNA amplification assay, and DNA digestion. Meanwhile, DNA exhibits great potential in the fabrication of new capillary-based biosensors and enzymatic bioreactors. Moreover, DNA has received significant research interest in improving capillary electrophoresis (CE) performance. We focus on highlighting the advantages of combining DNA and capillary-based microsystems. The general trend presented in this review suggests that the 'meeting' has offered a stepping stone for the application of DNA and capillary-based microsystems in the field of analytical chemistry.