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The limited replicability of retention data hinders its application in untargeted metabolomics for small molecule identification. While retention order models hold promise in addressing this issue, their predictive reliability is limited by uncertain generalizability. Here, we present the ROASMI model, which enables reliable prediction of retention order within a well-defined application domain by coupling data-driven molecular representation and mechanistic insights. The generalizability of ROASMI is proven by 71 independent reversed-phase liquid chromatography (RPLC) datasets. The application of ROASMI to four real-world datasets demonstrates its advantages in distinguishing coexisting isomers with similar fragmentation patterns and in annotating detection peaks without informative spectra. ROASMI is flexible enough to be retrained with user-defined reference sets and is compatible with other MS/MS scorers, making further improvements in small-molecule identification., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In recent decades, the global community has encountered several significant viral outbreaks, including the Ebola epidemic in West Africa, the Zika virus epidemic in South America, and the recent worldwide COVID-19 pandemic. In these instances, the deployment of effective vaccines has been instrumental in protecting public health. Nevertheless, as new challenges emerge in the prevention and management of infectious diseases, the traditional model of global vaccine development confronts both unprecedented opportunities and challenges. These circumstances underscore the limitations inherent in conventional vaccine development, particularly the protracted timelines and substantial costs involved. This article examines innovative approaches in contemporary vaccine clinical trials, investigates randomization techniques specific to vaccine studies, and delineates essential statistical considerations pertinent to vaccine trial design. The objective is to provide scientific support for vaccine development and to foster ongoing innovation and optimization within the realm of vaccine research and development.

Chip rate estimation for direct-sequence spread spectrum (DSSS) signals plays a crucial role in signal detection and interference identification in non-cooperative wireless communication systems. However, accurate chip rate estimation is difficult in low signal-to-noise ratio (SNR) environments due to the influence of noise and channel fading. To address this problem, an improved chip rate estimation method, based on a time-reassigned multisynchrosqueezing transform energy squeeze, for DSSS signals is proposed for low SNR conditions. In this method, we explain how to choose an appropriate wavelet function and concentrate the wavelet coefficients on the energy ridge by reordering time details. This enhances the time resolution of the signal energy, reduces noise interference, and improves the accuracy of chip rate estimation for DSSS signals. To validate the proposed method, we compared the effects of different information code lengths, spread spectrum code lengths, spread spectrum code sequences, and modulation schemes on chip rate estimation performance with traditional methods. Additionally, we applied the method to real DSSS signal data to demonstrate its feasibility. Simulation examples and measurements demonstrate the reliability of the proposed method in low SNR environments.

Land use in urban agglomerations is the main source of carbon emissions, and reducing them and improving land use efficiency are the keys to achieving sustainable development goals (SDGs). To advance the literature on densely populated cities and highly commercialized regions, this research evaluates the total-factor carbon emission efficiency index (TCEI) of 27 cities in China's Yangtze River Delta (YRD) urban agglomeration at different stages from 2011 to 2020 using two-stage dynamic data envelopment analysis (DEA). The study carries out regression analysis and a long-short-term memory model (LSTM) to respectively filter out the factors and predict TCEI. The results indicate the following. (1) The total efficiency of 27 cities has significantly improved from 2011 to 2020, and there are obvious spatial heterogeneity characteristics. (2) In terms of stages, most cities' efficiency values in the initial stage (energy consumption) exceed those in the second stage (sustainable land utilization). (3) In terms of influencing factors, urban green space's ability to capture carbon has a notably positive correlation with carbon emission efficiency. In contrast, the substantial carbon emissions resulting from human respiration are a negative factor affecting carbon emission efficiency. (4) Over the forthcoming six years, the efficiency value of land use TCEI in the YRD urban cluster is forecasted to range between 0.65 and 0.75. Those cities with the highest performance are projected to achieve an efficiency value of 0.9480. Lastly, this research investigates the interaction between actors and land resources on TCEI, resulting in a beneficial understanding for the former to make strategic adjustments during the urbanization process., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this work, by employing powders sourced directly from the original ingot for additive manufacturing, we enabled a comparative overview of the performance between CoCrMo manufactured via laser powder bed fusion (LPBF) and those in their original cast condition. Microstructural analysis revealed that the cast (CT) alloy predominantly consisted of coarse grains with distribution of sigma phase, while the LPBF process resulted in a refined grain structure devoid of the sigma phase. The tensile strength tests demonstrated that the LPBF-derived CoCrMo alloy had substantially greater tensile strength, and ductility compared to CT alloy. Corrosion tests indicated superior corrosion resistance in the LPBF alloy, albeit with a lower metal ion release. In vitro assays confirmed that LPBF CoCrMo alloys displayed favorable cytocompatibility. Consequently, it is concluded that the CoCrMo alloy processed through laser powder bed fusion exhibited enhanced mechanical performance and corrosion resistance. These improvements are primarily attributed to the transformation of the original coarse columnar grain structure through the LPBF technique., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 10 5 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N -methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.

Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules ( Ir-2 , Ir-2-1 ∼ Ir-2-4 ) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy) 2 (osip)] (PF 6 ) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule Ir-2 , incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes Ir-2-1 ∼ Ir-2-4 demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 μs for Ir-2-4 .

Prior research show that relative deprivation can decrease individuals' psychological well-being. However, the underlying mechanism between relative deprivation and psychological well-being remains unclear. To explore the mediating effects of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being. 426 undergraduate students submitted the online survey that assessed their psychological well-being, relative deprivation, self-efficacy and self-control. Students experienced high levels of psychological well-being, moderate to high levels of relative deprivation and moderate levels of self-efficacy and self-control. Parallel mediators of self-efficacy and self-control on the relationship between relative deprivation and psychological well-being were significant (each p < 0.01). This study explores the underlying mechanism between relative deprivation and psychological well-being by identifying the parallel mediators of self-efficacy and self-control. Effective interventions should be taken to alleviate students' relative deprivation and promote their self-efficacy, self-control and psychological well-being during future pandemics., (© 2024. The Author(s).)

This study aims to mine the genes of Dendrobium officinale in response to high temperature stress and explore the molecular mechanism underlying the heat tolerance of D. officinale. In this study, the D. officinale variety &quot;Dahongshe&quot; was exposed to high temperature for 0, 2, 6, and 12 h, and then transcriptome analysis and qPCR were carried out. The transcriptome of each sample was analyzed by high-throughput sequencing. A total of 14 639 transcripts were obtained after the assembly by StringTie, with the lengths ranging from 500 bp to 2 000 bp. A total of 1 858 differentially expressed genes(DEGs) under high temperature stress in D. officinale, including 1 085 genes with upregulated expression and 773 with downregulated expression. The number of DEGs gradually increased over the time of high temperature treatment. GO enrichment analysis showed that the DEGs were mainly concentrated in transmembrane transport, responses to light, temperature, and radiation stimuli, and activity of transcription factors. The KEGG enrichment analysis revealed that the DEGs responding to high temperature stress were mainly in the pathways of endoplasmic reticulum protein processing, phytohormone signaling pathways, and plant-pathogen interaction. qPCR was performed for 12 randomly selected DEGs, and the outcomes proved that the transcriptome data were accurate and reliable. The results provide a theoretical basis for future work on the molecular mechanism of heat tolerance and the breeding of heat-tolerant varieties of D. officinale.

Global climate change and the collection of environmental protection taxes are accelerating the green transformation of thermal power enterprises. This study selected Chinese thermal power listed companies as samples and used a dynamic three-stage (operational, green transformation, and market performance) network DEA model to evaluate their transformation efficiency and corporate performance. This paper incorporates targeted indicators such as ESG (environment, society, governance) and stock prices into the model and conducts a comparative study on the basis of macro policies and the geographical location of the enterprise. A comparative analysis was conducted on the efficiency of enterprises before and after the adjustment of the environmental tax burden, using the environmental tax burden as an exogenous variable. Thus, the following conclusions can be drawn: there is a certain positive correlation between the collaborative efficiency of the two links of thermal power enterprises and the economic development of their respective regions. Moreover, the green transformation efficiency of most thermal power enterprises is superior to the market performance efficiency. The environmental tax burden mainly improves the overall efficiency of thermal power enterprises by improving their operational efficiency and efficiency in the green transformation stage without affecting market performance. To further improve efficiency, thermal power enterprises should actively communicate with stakeholders to strive for more financial relief., (© 2024. The Author(s).)

Rationale: Myelin oligodendrocyte glycoprotein (MOG) antibody-related disease is a relatively recent entity in inflammatory demyelinating disease. Its clinical presentation varies in severity and the lack of specific imaging features makes it easy to misdiagnose. We now report the case of a MOG antibody-positive patient who presented with diplopia and dizziness, and whose brain magnetic resonance imaging (MRI) showed abnormal signals in the bilateral pontine brachium., Patient Concerns: A previously healthy 52-year-old woman presented with diplopia and dizziness, and was hospitalized 4 days after onset., Diagnoses: Brain MRI demonstrated abnormal hyperintense signals in the bilateral pontine brachium on T2-weighted fluid attenuated inversion recovery imaging. MRI enhancement showed abnormal enhancement foci in bilateral pontine brachium and pons. Cerebrospinal fluid examination showed Oligoclonal IgG bands were negative. The IgG index was normal, and serum aquaporin-4 antibody was negative, while serum MOG-Ab was positive (1:100). In conjunction with a positive serum MOG antibody and exclusion of other diseases, diagnosis of MOG antibody-related disease was made., Interventions: Intravenous methylprednisolone followed by oral corticosteroids., Outcomes: Symptoms resolved completely. At 4-month follow-up. Follow-up after 4 months showed disappearance of the abnormal signal in the left pontine brachium and diminution of abnormal high signal in the right compared to the previous one, and there was no recurrence 1 year after the onset of the disease., Lessons: If brain MRI indicating bilateral, multiple, and diffuse abnormal signals in the pontine brachium, and a discrepancy between the clinical symptoms and the imaging severity, a diagnosis of demyelinating disease should be considered highly probable. In such cases, anti-MOG antibody testing is essential for further defining the etiology. The clinical phenotype and imaging manifestations of MOG antibody-positive brainstem encephalitis may lack sufficient specificity to be readily identifiable. Timely diagnosis and early glucocorticoid therapy are beneficial in improving prognosis and preventing recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management., (© 2024 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)

Aerobic methane oxidation coupled with denitrification (AME-D) has garnered significant attention as a promising technology for nitrogen removal from water. Effective biofilm management on the membrane surface is essential to enhance the efficiency of nitrate removal in AME-D systems. In this study, we introduce a novel and scalable layer-structured membrane (LSM) developed using a meticulously designed polyurethane sponge. The application of the LSM in advanced biofilm management for AME-D resulted in a substantial enhancement of denitrification performance. Our experimental results demonstrated remarkable improvements in nitrate-removal flux (92.8 mmol-N m -2 d -1 ) and methane-oxidation rate (325.6 mmol m -2 d -1 ) when using an LSM in a membrane biofilm reactor (L-MBfR) compared with a conventional membrane reactor (C-MBfR). The l-MBfR exhibited 12.4-, 6.8- and 3.4-fold increases in nitrate-removal rate, biomass-retention capacity, and methane-oxidation rate, respectively, relative to the control C-MBfR. Notably, the l-MBfR demonstrated a 3.5-fold higher abundance of denitrifying bacteria, including Xanthomonadaceae, Rhodocyclaceae, and Methylophilaceae. In addition, the denitrification-related enzyme activity was twice as high in the l-MBfR than in the C-MBfR. These findings underscore the LSM's ability to create anoxic/anaerobic microenvironments conducive to biofilm formation and denitrification. Furthermore, the LSM exhibited a unique advantage in shaping microbial community structures and facilitating cross-feeding interactions between denitrifying bacteria and aerobic methanotrophs. The results of this study hold great promise for advancing the application of MBfRs in achieving efficient and reliable nitrate removal through the AME-D pathway, facilitated by effective biofilm management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear., Method: Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity., Results: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side., Conclusion: Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: According to the trend of global population aging, the proportion of elderly patients with chronic kidney disease (CKD) is expected to increase. However, there are more than 20 million people in China with decompensated kidney function, of which 19.25% are elderly people. Therefore, special attention should be paid to the education years, sleep quality, anxiety status, comorbidities with diabetes, cardiovascular disease (CVD), and anemia as independent risk factors for depression in elderly CKD patients. This study explores the clinical mana-gement of elderly CKD patients that should address these risk factors to prevent depression and improve their prognosis., Aim: To investigate depression risk factors in older patients receiving peritoneal dialysis, aiding future prevention of depression in these patients., Methods: This retrospective study included a primary study population of 170 patients with CKD who received peritoneal dialysis from January 2020 to December 2022. We assessed the patients' mental status using the Beck Depression Inventory Score-II (BDI-II), Self-Rating Anxiety Scale (SAS), Anxiety Inventory Score, and the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was employed to identify depression independent risk factors among these patients., Results: The non-depressed group had a significantly longer education period than the depressed group ( P < 0.05). The depressed group exhibited significantly higher mental status scores than the non-depressed group ( P < 0.001). Patients with diabetes mellitus (DM) or CVD had a higher probability of developing dep-ression. Patients with depression had significantly lower hemoglobin and albumin levels than patients without depression ( P < 0.05). Spearman correlation analysis of BDI-II scale scores, measuring depression, indicated positive correlations with BDI-II and SAS scores as risk factors for depression in patients with CKD. In contrast, years of education, hemoglobin levels, and peritoneal Kt/V were negatively correlated, serving as protective factors against depression. An analysis of variance for influences with significant differences in the univariate analysis revealed that years of schooling, BDI-II, SAS, PSQI, DM, CVD, and hemoglobin levels independently influenced depression in older patients with CKD., Conclusion: Education, BDI-II, SAS, PSQI, DM, and CVD are independent risk factors for depression in older patients with CKD; therefore, post-treatment psychological monitoring of high-risk patients is crucial to prevent depression., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

It has been demonstrated that diabetes cause neurite degeneration in the brain and cognitive impairment and neurovascular interactions are crucial for maintaining brain function. However, the role of vascular endothelial cells in neurite outgrowth and synaptic formation in diabetic brain is still unclear. Therefore, present study investigated effects of brain microvascular endothelial cells (BMECs) on high glucose (HG)-induced neuritic dystrophy using a coculture model of BMECs with neurons. Multiple immunofluorescence labelling and western blot analysis were used to detect neurite outgrowth and synapsis formation, and living cell imaging was used to detect uptake function of neuronal glucose transporters. We found cocultured with BMECs significantly reduced HG-induced inhibition of neurites outgrowth (including length and branch formation) and delayed presynaptic and postsynaptic development, as well as reduction of neuronal glucose uptake capacity, which was prevented by pre-treatment with SU1498, a vascular endothelial growth factor (VEGF) receptor antagonist. To analyse the possible mechanism, we collected BMECs cultured condition medium (B-CM) to treat the neurons under HG culture condition. The results showed that B-CM showed the same effects as BMEC on HG-treated neurons. Furthermore, we observed VEGF administration could ameliorate HG-induced neuronal morphology aberrations. Putting together, present results suggest that cerebral microvascular endothelial cells protect against hyperglycaemia-induced neuritic dystrophy and restorate neuronal glucose uptake capacity by activation of VEGF receptors and endothelial VEGF release. This result help us to understand important roles of neurovascular coupling in pathogenesis of diabetic brain, providing a new strategy to study therapy or prevention for diabetic dementia. Hyperglycaemia induced inhibition of neuronal glucose uptake and impaired to neuritic outgrowth and synaptogenesis. Cocultured with BMECs/B-CM and VEGF treatment protected HG-induced inhibition of glucose uptake and neuritic outgrowth and synaptogenesis, which was antagonized by blockade of VEGF receptors. Reduction of glucose uptake may further deteriorate impairment of neurites outgrowth and synaptogenesis., (© 2023. The Author(s).)

Background: Diabetic nephropathy (DN) is frequently seen in the development of diabetes mellitus, and its pathogenic factors are complicated. Its current treatment is controversial, and there is a lack of a relevant efficacy prediction model., Aim: To determine the effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with DN and chronic renal failure (CRF), and to construct an efficacy prediction model., Methods: We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022. We selected 94 patients who met the inclusion and exclusion criteria. Patients were assigned to a dialysis group ( n = 45) and a joint group ( n = 49) in relation to therapeutic regimen. The clinical efficacy of the two groups was compared after treatment. The changes in laboratory indexes after treatment were evaluated, and the two groups were compared for the incidence of adverse reactions. The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed., Results: The dialysis group showed a notably worse improvement in clinical efficacy than the joint group ( P = 0.017). After treatment, the joint group showed notably lower serum levels of serum creatinine, uric acid (UA) and blood urea nitrogen (BUN) than the dialysis group ( P < 0.05). After treatment, the joint group had lower serum levels of phosphorus, procollagen type I amino-terminal propeptide (PINP) and intact parathyroid hormone than the dialysis group, but a higher calcium level ( P < 0.001). Both groups had a similar incidence of adverse reactions ( P > 0.05). According to least absolute shrinkage and selection operator regression analysis, UA, BUN, phosphorus and PINP were related to treatment efficacy. According to further comparison, the non-improvement group had higher risk scores than the improvement group ( P < 0.0001), and the area under the curve of the risk score in efficacy prediction was 0.945., Conclusion: For treatment of CRF and DN, combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients, with good safety., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions., Purpose: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products., Methods: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products., Results: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products., Conclusion: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Reactive astrocytes can be transformed into new neurons. Vascular endothelial growth factor (VEGF) promotes the transformation of reactive astrocytes into neurons in ischemic brain. Therefore, in this study, the molecular mechanism of VEGF's effect on ischemia/hypoxia-induced astrocyte to neuron transformation was investigated in the models of rat middle cerebral artery occlusion (MCAO) and in astrocyte culture with oxygen and glucose deprivation (OGD). We found that VEGF enhanced ischemia-induced Pax6, a neurogenic fate determinant, expression and Erk phosphorylation in reactive astrocytes and reduced infarct volume of rat brain at 3 days after MCAO, which effects could be blocked by administration of U0126, a MAPK/Erk inhibitor. In cultured astrocytes, VEGF also enhanced OGD-induced Erk phosphorylation and Pax6 expression, which was blocked by U0126, but not wortmannin, a PI3K/Akt inhibitor, or SB203580, a MAPK/p38 inhibitor, suggesting VEGF enhanced Pax6 expression via activation of MAPK/Erk pathway. OGD induced the increase of miR365 and VEGF inhibited the increase of OGD-induced miR365 expression. However, miR365 agonists blocked VEGF-enhanced Pax6 expression in hypoxic astrocytes, but did not block VEGF-enhanced Erk phosphorylation. We further found that VEGF promoted OGD-induced astrocyte-converted to neuron. Interestingly, both U0126 and Pax6 RNAi significantly reduced enhancement of VEGF on astrocytes-to-neurons transformation, as indicated Dcx and MAP2 immunopositive signals in reactive astrocytes. Moreover, those transformed neurons become mature and functional. We concluded that VEGF enhanced astrocytic neurogenesis via the MAPK/Erk-miR-365-Pax6 signal axis. The results also indicated that astrocytes play important roles in the reconstruction of neurovascular units in brain after stroke., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory reaction, which is rare and life-threatening. According to the pathogen, HLH is divided into genetic and acquired. The most common form of acquired HLH is infection-associated HLH, of which Herpes viruses, particularly Epstein-Barr virus (EBV), are the leading infectious triggers. However, it is difficult to distinguish between simple infection with EBV and EBV-induced infection-associated HLH since both can destroy the whole-body system, particularly the liver, thereby increasing the difficulty of diagnosis and treatment., Case Summary: This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury, aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH. The patient was categorized as acquired hemophagocytic syndrome in adults. After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response, gamma globulin enhanced immunotherapy, the patient recovered., Conclusion: From the diagnosis and treatment of this patient, attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients' survival., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study quantitatively investigated the effect of dissolved oxygen (DO) concentration on aerobic denitrification, and showed the mechanism of aerobic denitrification from the perspective of electron competition by cultivating Pseudomonas stutzeri T13, a typical aerobic denitrifier, in an oxygen-based membrane biofilm reactor (O 2 -based MBfR). The experiments showed that when the O 2 pressure increased from 2 to 10 psig , the average effluent DO concentration during steady-state phases increased from 0.02 to 4.23 mg/L, and the corresponding mean NO 3 - -N removal efficiency slightly decreased from 97.2 % to 90.9 %. Compared to the maximum theoretical flux of O 2 in various phases, the actual O 2 transfer flux increased from a limited status (2.07 e - eq m -2 d -1 at 2 psig) to an excessive status (5.58 e - eq m -2 d -1 at 10 psig). The increase of DO inhibited the electron availability for aerobic denitrification, which decreased from 23.97 % to 11.46 %, accompanying the increased electron availability for aerobic respiration from 15.87 % to 28.36 %. Unlike the napA and norB genes, the expression of the nirS and nosZ genes was significantly affected by DO, with the highest relative fold-changes of 6.5 and 6.13 at 4 psig O 2 , respectively. The results contribute to clarifying the mechanism of aerobic denitrification from the quantitative perspective of electron distribution and the qualitative perspective of gene expression, which benefits the control and practical application of aerobic denitrification for wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-coding RNAs are crucial for cancer progression, among which miR-34c-3p has been demonstrated to be a tumor suppressor in non-small cell lung cancer (NSCLC). In this study, we attempt to identify flavonoids that can up-regulate miR-34c-3p expression, evaluate the anticancer activity of the flavonoids and explore its underlying mechanism in NSCLC cells. Six flavonoids were screened by RT-qPCR and we found that jaceosidin significantly increased miR-34c-3p expression in A549 cells. We found that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner, indicated by cell counting kit (CCK-8) assay, wound healing assay, transwell assay and EdU assay, we observed that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner. Further research suggested that miR-34c-3p bound to the transcriptome of integrin α2β1 and then inhibited its expression, leading to the inhibitory effect on the migration and invasion of NSCLC. Our study sheds some light on anti-tumor of jaceosidin and provides a potential lead compound for NSCLC therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Two-photon photodynamic therapy (TP-PDT), as a new method for cancer, has shown unique advantages in tumors. A low two-photon absorption cross-section (δ) in the biologic spectral window and a short triplet state lifetime are the important issues faced by the current photosensitizers (PSs) in TP-PDT. In this paper, the photophysical properties of a series of Ru(II) complexes were studied by density functional theory and time-dependent density functional theory methods. The electronic structure, one- and two-photon absorption properties, type I/II mechanisms, triplet state lifetime, and solvation free energy were calculated. The results showed that the substitution of methoxyls by pyrene groups greatly improved the lifetime of the complex. Furthermore, the addition of acetylenyl groups subtly enhanced δ. Overall, complex 3b possess a large δ(1376 GM), a long lifetime (136 μs), and better solvation free energy. It is hoped that it can provide valuable theoretical guidance for the design and synthesis of efficient two-photon PSs in the experiment.

China's immunization programme is relatively strong, with latest WHO-UNICEF monitoring rates for 2019 showing national vaccination coverage over 90%. However, vaccination coverage is heterogeneous, varying across geographic regions, rural-urban communities, and sub-populations. We conducted a qualitative study from a critical realist perspective, analyzing semi-structured interviews with 26 vaccination providers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. We analyzed data thematically, using deductive and inductive coding. Providers reported vaccination coverage in their areas had increased significantly, but remained lower among migrant and left-behind children. Main coverage determinants were child-related (i.e. gender, number, health status), caregiver-related (i.e. socioeconomic status, role, education level, ethnicity), institution-related (i.e. vaccinator numbers, information system, appointment process), and system-related (i.e. vaccine supply, intersectoral cooperation, vaccine 'hesitancy'). Potentially effective measures to promote vaccination coverage included using routine maternal and child health-care visits for catch-up vaccination, providing additional health education, conducting follow-up family visits by village doctors, and requiring vaccination verification at school enrollment. This is the first qualitative study to examine potential determinants of low vaccination coverage in these areas of China. Findings can inform policies to strengthen the role of schools, develop the national immunization information system, and promote appointment apps. More consideration is needed to improve service quality and eliminating inequities, such as strengthening health education and service provision for migrant and left-behind children.

Aims: To develop a feasible and effective nurse-manager dualistic intervention program to support nurses coping with burnout symptoms., Background: Person-organization combined interventions were recommended as the most effective approach for reducing burnout symptoms. However, few interventions have been developed in the nursing field., Methods: The Medical Research Council, United Kingdom (MRC UK), Framework for Development and Evaluation of Complex Interventions, was employed for nurse-manager dualistic intervention program development. The following three steps were followed for developing the dualistic intervention program: (1) identifying the evidence base by conducting extensive reviews of the relevant literature and a mixed study; (2) identifying/developing a theory by selecting the job demands-resources model and proposing the theoretical framework for intervention development; and (3) modifying the process and outcomes of the nurse-manager dualistic intervention program., Results: The intervention program consists of six group sessions over 9 weeks. Researchers/managers are supposed to deliver the program. The main contents of the intervention are (1) inception (session 1); (2) discovery (session 2); (3) dream (session 3); (4) design (session 4); (5) destiny (session 5); and (6) keep (session 6). The emphasis of the intervention is on helping nurses dealing with burnout symptoms., Conclusion: Following the guidance of the MRC framework, a feasible and potentially effective nurse-manager dualistic intervention program was developed for nurses coping with burnout. Future studies are needed to model the intervention and assess the effects and replicability of the intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Wang, Yue, Sun, Ding and Jia.)

Objective: To investigate the baseline levels of microorganisms' growth on the hands of anesthesiologists and in the anesthesia environment at a cancer hospital., Methods: This study performed in nine operating rooms and among 25 anesthesiologists at a cancer hospital. Sampling of the hands of anesthesiologists and the anesthesia environment was performed at a ready-to-use operating room before patient contact began and after decontamination., Results: Microorganisms' growth results showed that 20% (5/25) of anesthesiologists' hands carried microorganisms (> 10 CFU/cm 2 ) before patient contact began. Female anesthesiologists performed hand hygiene better than did their male counterparts, with fewer CFUs ( P = 0.0069) and fewer species ( P = 0.0202). Our study also found that 55.6% (5/9) of ready-to-use operating rooms carried microorganisms (> 5 CFU/cm 2 ). Microorganisms regrowth began quickly (1 hour) after disinfection, and increased gradually over time, reaching the threshold at 4 hours after disinfection. Staphylococcus aureus was isolated from the hands of 20% (5/25) of anesthesiologists and 33.3% (3/9) of operating rooms., Conclusion: Our study indicates that male anesthesiologists need to pay more attention to the standard operating procedures and effect evaluation of hand hygiene, daily cleaning rate of the operating room may be insufficient, and we would suggest that there should be a repeat cleaning every four hours., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Aerobic methane oxidation coupled with denitrification (AME-D) executed in membrane biofilm bioreactors (MBfRs) provides a high promise for simultaneously mitigating methane (CH 4 ) emissions and removing nitrate in wastewater. However, systematically experimental investigation on how oxygen partial pressure affects the development and characteristics of counter-diffusional biofilm, as well as its spatial stratification profiles, and the cooperative interaction of the biofilm microbes, is still absent. In this study, we combined Optical Coherence Tomography (OCT) with Confocal Laser Scanning Microscopy (CLSM) to in-situ characterize the development of counter-diffusion biofilm in the MBfR for the first time. It was revealed that oxygen partial pressure onto the MBfR was capable of manipulating biofilm thickness and spatial stratification, and then managing the distribution of functional microbes. With the optimized oxygen partial pressure of 5.5 psig (25% oxygen content), the manipulated counter-diffusional biofilm in the AME-D process obtained the highest denitrification efficiency, due mainly to that this biofilm had the proper dynamic balance between the aerobic-layer and anoxic-layer where suitable O 2 gradient and sufficient aerobic methanotrophs were achieved in aerobic-layer to favor methane oxidation, and complete O 2 depletion and accessible organic sources were kept to avoid constraining denitrification activity in anoxic-layer. By using metagenome analysis and Fluorescence in situ hybridization (FISH) staining, the spatial distribution of the functional microbes within counter-diffused biofilm was successfully evidenced, and Rhodocyclaceae, one typical aerobic denitrifier, was found to survive and gradually enriched in the aerobic layer and played a key role in denitrification aerobically. This in-situ biofilm visualization and characterization evidenced directly for the first time the cooperative path of denitrification for AME-D in the counter-diffused biofilm, which involved aerobic methanotrophs, heterotrophic aerobic denitrifiers, and heterotrophic anoxic denitrifiers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Feline calicivirus (FCV), Feline panleukopenia virus (FPV), and Feline herpesvirus type I (FHV-1) are the three most common pathogens in cats, and also are the main pathogens leading to the death of kittens. Here, by a combination of gold nanoparticles and conventional PCR, we established a novel triple NanoPCR molecular detection method for clinical detection., Results: The triple NanoPCR molecular detection is able to detect 2.97 × 10 1 copies/μL FCV recombinant copies plasmid per reaction, 2.64 × 10 4 copies/μL FPV recombinant copies plasmid per reaction, and 2.85copies/μL FHV-1 recombinant copies plasmid per reaction at the same time. The sensitivity of each plasmid is 100 times, 10 times, and 100 times higher than conventional PCR, respectively. The clinical results showed that among the 38 samples, the positive rates of FCV, FPV, and FHV-1 in a NanoPCR test were 63.16, 31.58, and 60.53%, while in a conventional PCR were 39.47, 18.42, and 34.21%., Conclusions: In this report, it is the first time that NanoPCR assays are applied in the detection of FCV, FPV, and FHV-1 as well. This sensitive and specific NanoPCR assay can be widely used in clinical diagnosis and field monitoring of FCV, FPV, and FHV-1 infections., (© 2022. The Author(s).)

Angiogenic factors play an important role in protecting, repairing, and reconstructing vessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34 + vascular length and area. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury, and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.

Hematopoiesis plays an important role(s) in maintenance and physiology of life. Hematopoiesis in vertebrates mainly includes self-renewal of the hematopoietic stem cells, proliferation and differentiation of the hematopoietic progenitor cells, and maturation of the blood cells. The regulation of hematogenesis involves a variety of transcription factors, membrane receptors, hematopoietic growth factors, and microRNAs, which interact with each other and form a variety of signaling pathways and signal networks. MicroRNAs are a class of non-coding RNAs widely distributed in eukaryotic cells and play important roles in the hematopoietic process. The expression of microRNAs is regulated by transcription factors involved in hematopoietic signaling pathways. In turn, their expression can inhibit or down-regulate those of transcription factors involved in hematopoietic related signaling pathways and other related regulatory factors, thereby affecting the signaling pathways related to hematopoiesis and ultimately the hematopoietic process. In this review, we introduce the hematopoiesis processes and related signal pathways in vertebrates, focusing on the relationships between microRNAs and hematopoietic transcription factors and signal pathways, and summarizing the recent research progress of microRNAs in hematopoiesis.

Background: Peritoneal dialysis (PD) is the main renal replacement therapy in elderly patients account for hemodynamic stability. The clinical characteristics and prognosis of elderly PD patients are varies in different dialysis centers. We analyzed the characteristics, outcomes and prognosis factors of survival in elderly PD patients in China, to better understand their status and improve their quality of life., Methods: This prospective, observational study categorized 202 PD patients by age: elderly group ≥65 years, younger group <65 years. The inclusion criteria were: age >18 years, first PD treatment and dialysis time >3 months, and complete data. Clinical characteristics including demographic data, hemodynamic variables were compared between groups. After a median follow-up of 44 months, prognosis outcomes between young and elderly groups were measured. Multivariate Cox regression analysis were used to establish the models for predicting outcomes. Then the nomogram of the model was generated., Results: A total of 202 PD patients were enrolled: 61 in the elderly group and 141 in the younger group. The comparison of baseline data revealed decreased serum albumin, normalized protein catabolic rate and higher incidence of previous cardiovascular, cerebrovascular diseases, Charlson Comorbidity Index (CCI) in the elderly group. The mortality rate was substantially higher in the elderly group. Cardiovascular disease was the main cause of death in elderly PD patients. High body mass index (BMI) [hazard ratio (HR) =1.0, 95% confidence interval (CI): 1.0-1.1, P=0.005], high CCI (HR =1.1, 95% CI: 1.0-1.2, P=0.022), and ischemic heart disease (ISD) (HR =2.5, 95% CI: 1.0-6.1, P=0.042) were risk factors for the long-term survival of elderly PD patients., Conclusions: High BMI, high CCI and ISD were important factors for evaluating the adverse outcomes of elderly PD patients. Larger studied are needed to identify risk factors in elderly PD patients and to improve their outcomes.

Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01E vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01E were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01E included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning., Competing Interests: I have read the journal’s policy, and the authors of this manuscript have the following competing interests: Rebecca Harris reports current employment by Sanofi Pasteur; her Sanofi employment includes work on COVID-19, but is unrelated to TB., (Copyright: © 2022 Pelzer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Kudoa (Myxosporea: Multivalvulida) parasites are critical pathogens in marine and freshwater fish associated with significant economic losses and reduced market prices caused by post-mortem myoliquefaction or numerous cysts on muscles. In the present study, large yellow croakers infected by Kudoa were found during fish disease surveillance in China in November 2020 and used for morphological observation and characterization using light DIC microscopy and electron microscopy. Numerous creamy-white oval plasmodia were observed in muscles and on the surface of brain cartilage, gill arches, and serosal surfaces. The spores were considerably longer and thicker than previously reported Kudoa , with protruding polar filaments (PFs) in the mature spores, fingertip-shaped apical projections (APs), and polar capsules. Phylogenetic analyses with SSU rDNA, LSU rDNA, and mitochondrial DNA showed that the Kudoa -infected sample (LcK-2020) had the highest similarity to Kudoa iwatai reported in Japan. Based on the morphological characterization and phylogenetic analysis, it could be concluded that the sample LcK-2020 was infected by Kudoa iwatai , which would be the first report of Kudoa iwatai infection in large yellow croaker in China.

Background: China experiences large variations in influenza seasonal activity. We aim to update and improve the current understanding of regional-based within-year variations of influenza activity across mainland China to provide evidence for the planning and optimisation of healthcare strategies., Methods: We conducted a systematic review and spatio-temporal meta-analysis to assess regional-based within-year variations of ILI outpatient consultation rates, influenza test positivity rates amongst both ILI outpatients and SARI inpatients, and influenza-associated excess mortality rates. We searched English and Chinese databases for articles reporting time-series data on the four influenza-related outcomes at the sub-national and sub-annual level. After synthesising the data, we reported on the mean monthly rate, epidemic onset, duration, peak and intensity., Results: We included 247 (7.7%) eligible studies in the analysis. We found within-year influenza patterns to vary across mainland China in relation to latitude and geographic location. High-latitude provinces were characterised by having short and intense annual winter epidemics, whilst most mid-latitude and low-latitude provinces experience semi-annual epidemics or year-round activity. Subtype activity varied across the country, with A/H1N1pdm09 and influenza B occurring predominantly in the winter, whereas A/H3N2 activity exhibited a latitudinal divide with high-latitude regions experiencing a winter peak, whilst mid and low-latitude regions experienced a summer epidemic. Epidemic onsets and peaks also varied, occurring first in the north and later in the southeast. We found positive associations between all influenza health outcomes. In addition, seasonal patterns at the prefecture and county-level broadly resembled their wider province., Conclusions: This is the first systematic review to simultaneously examine the seasonal variation of multiple influenza-related health outcomes at multiple spatial scales across mainland China. The seasonality information provided here has important implications for the planning and optimisation of immunisation programmes and healthcare provision, supporting the need for regional-based approaches to address variations in local epidemiology., (© 2022. The Author(s).)

Liver toxicity induced by Triptolide (TP) has limited its clinical application on rheumatoid arthritis (RA). Saponins have been proved as an efficacious remedy to mitigate hepatotoxicity. However, the mechanism of reducing hepatotoxicity by saponins intervention remains incompletely characterized. Tryptophan (Trp) metabolites activate transcriptional regulators to mediate host detoxification responses. Our study aimed to investigate whether Clematichinenoside AR (C-AR) could attenuate TP-induced liver damage by regulating Trp metabolism. We used targeted metabolomics to quantify Trp metabolites in the serum and liver samples of collagen-induced arthritis rats treated by TP. Multiple comparison analyses helped the evaluation of promising biomarkers. The pronounced changed levels of Trp, indole acetic acid, and indole-3-carboxaldehyde in the serum and indole acetic acid, indole, and tryptamine in the liver are relevant to TP-induced liver injury. Intervention with C-AR could relieve TP-induced hepatotoxicity evidenced by ameliorative serum parameters and hepatic histology. In addition, C-AR regulated the levels of these indoles biomarker candidates to normal. Therapeutic modulation with natural compounds might be a useful clinical strategy to ameliorate toxicity induced by TP. Deciphering Trp metabolism will facilitate a better understanding of the pathogenesis of diseases and drug responding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bovine respiratory disease complex (BRDC) is a serious disease affecting feedlot cattle in China and likely other places worldwide. Bovine viral diarrhea virus (BVDV) and bovine parainfluenza virus type 3 (BPIV3) are principally responsible for causing BRDC, and are a major strain to the industrial economy. Eradication of these viruses/disease requires swift viral identification and treatment. Hence, this study established a fast and easy procedure of BVDV and BPIV3 identification that employs reverse transcription recombinase polymerase amplification (RT-RPA) and lateral flow dipstick (LFD), and uses primers and lateral flow (LF) probe targeting the 5'-UTR gene of BVDV and phosphoprotein P gene of BPIV3, respectively. Our assay was able to successfully amplify BVDV and BPIV3 RNA within 25 min at 35 °C using RT-RPA, with products visible on the LFD within 5 min at room temperature (RT). The lowest detection limits were 50 RNA molecules for BVDV and 34 RNA molecules for BPIV3 per reaction. We also demonstrated that the established dual RT-RPA LFD assay was precise and targeted, harboring excellent potential to become an onsite molecular diagnostic tool in the detection of BVDV and BPIV3. This method can detect BVDV (Pestivirus A, B) and BPIV3, and exhibit no cross-reaction with other viruses like the classical swine fever virus (CSFV) and infectious bovine rhinotracheitis virus (IBRV). The assay performance was further assessed with clinical samples, and demonstrated good performance in comparison to real-time RT-PCR (RT-qPCR). Moreover, the RT-RPA LFD assay was comparitively rapid and required minimal training., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recommendations by health professionals are important for vaccines that are not included in national schedules. This study explored health professionals' perspectives on recommending non-scheduled (user-fee) childhood vaccinations in China, identifying key influences on professionals' interactions with caregivers. We conducted individual semi-structured interviews with 20 health professionals from three provinces in China and analyzed data thematically using deductive and inductive coding. Health professionals from all three provinces were uncomfortable about being perceived to encourage parents to accept vaccines that incurred a fee. They provided information about non-scheduled vaccines but emphasized parental autonomy in decision-making. Rural parents were less aware of unscheduled vaccines and health professionals were more likely to encourage parents living in more affluent areas to consider these vaccines; varicella vaccine was preferred by parents as a way of preventing school absence. Economic incentives for unscheduled vaccines were given to staff at most study sites, although the amount given varied widely. These variations meant that staff receiving lower incentives were not motivated to promote non-scheduled vaccines if their workload was high; on the contrary, those receiving higher incentives were more likely to promote these vaccines. Health professionals need more guidance on how to recommend unscheduled vaccines in an informative, positive and appropriate manner. It is evident that parents' awareness of these vaccines, and their economic circumstances, influence vaccinators recommendation practice. Economic incentives prompted health professionals to recommend non-scheduled vaccines; however, the application of such staff incentives varied widely in China. To adopt appropriate economic incentives, professional organizations should develop protocols for the use of incentives that account for their influence on recommendation practices. Suitable recommendation policy needs to balance basic salaries with performance-based incentives, consider overall workload, and include monitoring and evaluation of economic incentives.

Background: Sleep disorders are highly prevalent among stroke survivors and impede stroke recovery. It is well established that melatonin has neuroprotective effects in animal models of ischemic stroke. However, as a modulator of endogenous physiological circadian rhythms, the effects of melatonin on poststroke sleep disorders remain unclear. In the present study, we investigated how melatonin delivered intraperitoneally once daily in the subacute phase after stroke onset, influencing neuronal survival, motor recovery, and sleep-wake profiles in rats., Methods: Transient ischemic stroke in male Sprague-Dawley rats was induced with 30 min occlusion of the middle cerebral artery. Melatonin or vehicle was delivered intraperitoneally once daily in the subacute phase, from 2 to 7 days after stroke. Electroencephalogram and electromyogram recordings were obtained simultaneously., Results: Compared to the effects observed in the vehicle-treated ischemic group, after 6 daily consecutive treatment of melatonin at 10 mg/kg starting at ischemic/reperfusion day 2, the infarct volume was significantly decreased (from 39.6 to 26.2%), and the degeneration of axons in the ipsilateral striatum and the contralateral corpus callosum were significantly alleviated. Sensorimotor performances were obviously improved as evidenced by significant increases in the latency to falling off the wire and in the use of the impaired forelimb. In addition to those predictable results of reducing brain tissue damage and mitigating behavioral deficits, repeated melatonin treatment during the subacute phase of stroke also alleviated sleep fragmentation through reducing sleep-wake stage transitions and stage bouts, together with increasing stage durations. Furthermore, daily administration of melatonin at 9 a.m. significantly increased the nonrapid eye movement sleep delta power during both the light and dark periods and decreased the degree of reduction of the circadian index., Conclusions: Melatonin promptly reversed ischemia-induced sleep disturbances. The neuroprotective effects of melatonin on ischemic injury may be partially associated with its role in sleep modulation., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Vertical expansion makes the structure and pattern of the city more complicated. Traditional two-dimensional landscape pattern cannot completely reflect the ecological structure and functional characteristics of urban landscape. In this study, we used the three-dimensional landscape pattern metrics to quantify the regional three-dimensional landscape pattern, and used boosted regression tree (BRT) machine learning algorithms to comprehensively analyze the interaction between social-environmental factors and urban landscape patterns in the central part of Shanghai. Results showed that high building ratio, mean architecture height, and architecture height standard deviation had higher values in the surrounding area of the inner ring. The number of buildings and landscape shape index were higher in the outer ring than those in other area. Building coverage ratio, floor area ratio and Shannon's diversity index had higher values in the central part, with the metrics of Puxi being generally higher than those of Pudong. Population density and normalized vegetation index (NDVI) interacted most significantly with the three-dimensional landscape pattern, with GDP as the least influential factor. Within a certain range, the three-dimensional landscape pattern metrics increased with larger population density in the social factors, and decreased with lower rate of NDVI and water surface ratio in the environmental factors. Our results demonstrated that the BRT method was effective in quantifying the interaction between landscape pattern and social-environmental factors. Our results help improve the understanding of the relationship between ecological environment and human well-being in the central part of Shanghai and provide a scientific basis for the urban three-dimensional expansion planning.

Background: Massive community-wide testing has become the cornerstone of management strategies for the COVID-19 pandemic., Objective: This study was a comparative analysis between the United Kingdom and China, which aimed to assess public attitudes and uptake regarding COVID-19 testing, with a focus on factors of COVID-19 testing hesitancy, including effectiveness, access, risk perception, and communication., Methods: We collected and manually coded 3856 UK tweets and 9299 Chinese Sina Weibo posts mentioning COVID-19 testing from June 1 to July 15, 2020. Adapted from the World Health Organization's 3C Model of Vaccine Hesitancy, we employed social listening analysis examining key factors of COVID-19 testing hesitancy (confidence, complacency, convenience, and communication). Descriptive analysis, time trends, geographical mapping, and chi-squared tests were performed to assess the temporal, spatial, and sociodemographic characteristics that determine the difference in attitudes or uptake of COVID-19 tests., Results: The UK tweets demonstrated a higher percentage of support toward COVID-19 testing than the posts from China. There were much wider reports of public uptake of COVID-19 tests in mainland China than in the United Kingdom; however, uncomfortable experiences and logistical barriers to testing were more expressed in China. The driving forces for undergoing COVID-19 testing were personal health needs, community-wide testing, and mandatory testing policies for travel, with major differences in the ranking order between the two countries. Rumors and information inquiries about COVID-19 testing were also identified., Conclusions: Public attitudes and acceptance toward COVID-19 testing constantly evolve with local epidemic situations. Policies and information campaigns that emphasize the importance of timely testing and rapid communication responses to inquiries and rumors, and provide a supportive environment for accessing tests are key to tackling COVID-19 testing hesitancy and increasing uptake., Competing Interests: Conflicts of Interest: HJL is on the Merck Vaccine Confidence Advisory Board. Her research group, the Vaccine Confidence Project, received research grants from GSK and Merck on vaccine confidence issues. None of those research grants are related to this paper. The other authors have no conflicts to declare., (©Leesa Lin, Yi Song, Qian Wang, Jialu Pu, Fiona Yueqian Sun, Yixuan Zhang, Xinyu Zhou, Heidi J Larson, Zhiyuan Hou. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 27.08.2021.)

In China, there are two categories of vaccines available from the Chinese Center for Disease Control and associated public health agencies. Extended Program of Immunization (EPI) vaccines are government-funded and non-EPI vaccines are voluntary and paid for out-of-pocket. The government plans to transition some non-EPI vaccines to EPI in the coming years, which may burden public health system capacity, particularly in terms of budget, workforce, supply chains, and information systems. Our study explored vaccinator and caregiver perspectives on introducing non-EPI vaccines into routine immunization and perceived facilitators and barriers affecting this transition. We conducted a qualitative study from a realist perspective, analysing semi-structured interviews with 26 vaccination providers and 160 caregivers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. Data were analysed thematically, using deductive and inductive coding. Most participants were positive about adding vaccines to the national schedule. Candidate EPI vaccines most frequently recommended by participants were varicella, mumps vaccine, and hand-foot-mouth disease. Providers generally considered existing workspaces, cold-chain equipment, and funding sufficient, but described frontline staffing and vaccine information systems as requiring improvement. This is the first qualitative study to explore interest, barriers, and facilitators related to adding vaccines to China's national schedule from provider and caregiver perspectives. Findings can inform government efforts to introduce additional vaccines, by including efforts to retain and recruit vaccine programme staff and implement whole-process data management and health information systems that allow unified nationwide data collection and sharing.

Endevours on the enhancement of nitrate removal efficiency during methane oxidation coupled with denitrification (AME-D) has always overlooked the role of membrane employed. It would be highly beneficial to enrich the biomass content and to manage biofilm on the membrane, in the utilization of methane and denitrification. In this study, an innovative and scalable double-layer membrane (DLM) was designed and prepared for a membrane biofilm reactor (MBfR), to simultaneously enhance nitrate removal flux and methane utilization efficiency during aerobic methane oxidation coupled with the denitrification (AME-D) process. The DLM allowed quick bacterial attachment and biomass accumulation for biofilm growth, which would be then self-regulated for well distribution of functional microbes on/within the DLM. Upon a high biofilm density of over 70 g-VSS m -2 achieved on the DLM, the methane utilization efficiency of the MBfR was enhanced significantly to over 1.3 times than the control MBfR with conventional polypropylene membrane. The MBfR employed DLM also demonstrated the maximum nitrate removal flux of 740 mg-NO 3 - -N m -2 d -1 that was approximately 1.64 times of that in control MBfR at continuous-mode operation. This DLM indeed favored the enrichment of Type II aerobic methanotrophs of Methylocystaceae, and methanol-utilization denitrifiers of Rhodocyclaceae that preferentially utilize methanol as the cross-feeding intermediates to promote the methane utilization efficiency, and thus to enhance the nitrate removal flux. These results raised from new designed DLM confirmed the importance of membrane surface properties on the effectiveness of MBfR, and offered great potential to address challenging problems of MBfRs during engineering application., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application. Methods: The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results: The established method had a good Linearity ( R 2 >0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day ( n =5) RSDs and the inter-day ( n =15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8 + T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8 + T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8 + T cells have a higher level of RNA methylation. Conclusion: This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

The demonstration area of ecologically friendly development in the Yangtze River Delta is a major national strategy area, and thus eco-environmental protection should be a priority for the sustainable development. Exploring the spatial-temporal variations of franctional vegetation coverage (FVC) is conducive to accurate assessing the ecological quality of environment, which is of great significance to regional sustainable development. In this study, the characteristics and trends of spatial-temporal variation of vegetation cover during 1984-2019 in the demonstration area were analyzed based on Google Earth Engine (GEE). The effects of different ecological factors on FVC were quantified by the boosted regression tree (BRT). Results showed that,the changing trend of FVC in the study area shifted from decreasing to increasing trend from 1984 to 2019. The spatial distribution of FVC in the study area varied with both stages and regions. FVC was mainly degraded. Compared with the year 1984, the area of vegetation degradation and improvement in 2019 accounted for 49.8% and 12.8%, respectively. The vegetation degradation mainly occurred in the north of Wujiang, south of Jiashan, and northeast of Qingpu. Human activities severely weakened the influence of natural factors on FVC. Our findings suggested that the GEE is an effective tool for monitoring the dynamics of vegetation coverage.

Access to vaccination information could influence public attitudes towards vaccination. This study investigated the number and types of vaccination-related information sources, and estimated their associations with vaccine confidence and hesitancy in China. In January 2019, we conducted a cross-sectional survey in China, and 2122 caregivers with children <6 years completed self-administered questionnaires. Logistic regressions were used to assess associations between caregivers' primary information sources and vaccine confidence/hesitancy. A majority (72%) of caregivers had multiple sources of vaccination-related information. The proportions of caregivers reporting professional sources, media, and peers as primary information sources were 81%, 63%, and 26%. Internal migrants were less likely to get information from professional sources; more educated and wealthier caregivers reported more information sources and were more likely to get information from media and peers. Caregivers who reported professional information sources had significantly higher odds of being confident about the safety of vaccines and lower odds of being hesitant toward vaccination than those who did not. Caregivers who reported the media as a primary information source had significantly higher odds of being hesitant toward vaccination than those who did not. To address vaccine hesitancy, it is essential to promote universal access to professional vaccination-related information sources, and to use the media to disseminate evidence-based information and clarify misinformation. Health communication should target internal migrants, and more educated and wealthier caregivers.

Neurotransmitter (NT) abnormalities in the enteric nervous system have been reported as crucial roles to regulate the intestinal inflammation and gut immune homeostasis. Capturing quantitative changes at the NT metabolome provides an opportunity to develop an understanding of neuroimmune-mediated inflammation. Given the wide diversity of chemical characterizations in the NTs, only partial coverage of the NT metabolome can be simultaneously quantified in a single-run analysis. Herein, we summarized the distribution of functional groups of compound entries in the NT metabolome. Based on this information, an orthogonal dansyl-labeling and label-free dual pretreatment approach was separately designed to target phenol and amine NTs and tertiary amine and choline NTs. By combining the dansyl-labeled and unlabeled NTs within a single vial, a comprehensive and practical approach was optimized for quantifying high coverage of NT metabolome in a single-run analysis on the reversed-phase C18 column. Method validation indicated good linearity with correlation coefficients (R 2 ) > 0.99, intra- and interday accuracy with relative error < ±20%, and precision with relative standard deviations of ≤15%. With this method, we could simultaneously monitor the alterations of cholines, amines, amino acids, tryptophan and phenylalanine biological pathways in dextran sulphate sodium-induced colitis mice. The measured levels of NT metabolome ranged from 0.0007 to 3.540 μg/mg in intestinal contents and 0.013-154.54 μg/mL in serum samples. The NT metabolism was disrupted by colitis, characterized by the changed NT levels in serum and excessive amino acid NTs accumulation in the intestinal contents. We envisage that the orthogonal approach is of great significance for the comprehensive determination of targeted metabolomics. NTs have the potential to be biomarkers for clinical metabolomics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Vaccine hesitancy is cited as one of the top threats to global health. The Changchun Changsheng Biotechnology Company was found to have violated good manufacturing practices in July 2018, leading to widespread distribution of sub-potent vaccines in China. We estimated the prevalence and determinants of vaccine hesitancy following the Changchun Changsheng vaccine incident (CCVI)., Methods: We conducted a cross-sectional survey in China in January 2019, and 2,124 caregivers of children < 6 years old completed self-administered questionnaires. Multinomial logistic regression was used to assess the determinants of vaccine hesitancy; the potential determinants included demographics, socioeconomic status, vaccine confidence, and knowledge of the CCVI. Adjusted Odds Ratios (AORs) and 95% confidence intervals (CI) are reported., Results: Around 89% of caregivers had heard of the CCVI. Although 83% and 88% of caregivers agreed that vaccines are safe and effective, respectively, 60% expressed some hesitancy about vaccination. Of those hesitant, 26% vaccinated their children at times with doubts, 31% delayed vaccination and 3% refused specific vaccines. Multinomial regression analysis showed that confidence in vaccine safety was associated with a reduced odds of doubts on vaccination (AOR = 0.64; 95%CI = 0.44-0.94), whereas caregivers who had heard of the CCVI had a significantly higher odds of doubts on vaccination (AOR = 1.61; 95%CI = 1.05-2.45). Confidence in the vaccine delivery system and government were associated with a lower odds of vaccine hesitancy. Caregivers with higher education and Buddhism or other religions were significantly more hesitant to vaccinate their children., Conclusion: Vaccine hesitancy was prevalent following the CCVI. Over half the caregivers either accepted childhood vaccination with doubts or delayed vaccines; only a small number were active refusers. Our findings highlight the importance of addressing vaccine hesitancy, especially following vaccine incidents. Tailored communications are needed to reduce vaccine hesitancy, especially among the highly educated and Buddhist caregivers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: A full spectrum of video capsule endoscopy (VCE) adverse events over the past two decades has not been evaluated. We aimed to determine pooled rates, predictors and temporal-trend of VCE adverse events over the past two decades., Methods: Systematic search of PubMed and EMBASE for English-language publications reporting VCE adverse events (January 1, 2000 to March 31, 2019). Data were extracted independently by two investigators. Pooled VCE adverse event rates were calculated using the random or fixed model as appropriate. Predictors and temporal-trend of each adverse event were performed by meta-regression analyses., Results: In total, 402 studies were identified, including 108,079 VCE procedures. Rate of retention, swallow disorder, aspiration, technical failure, and procedural adverse events were 0.73% (95% confidence interval [CI] 0.59-0.89%), 0.75% (95% CI 0.43-1.13%), 0.00% (95% CI 0.00-0.00%), 0.94% (95% CI 0.65-1.28%), 0.67% (95% CI 0.32-1.10%), respectively; incomplete examination rate of esophagus, stomach, small bowel, and colon were 9.05%, 7.69%, 12.08%, 19.19%, respectively. Patency capsule reduced retention rate by 5.04%, whereas known inflammatory bowel disease increased retention rate by 4.29%. Elder was the risk and protective factor for small bowel incomplete examination (0.30%) and swallow disorder (- 0.72%), respectively. Rates of retention and small bowel incomplete examination significantly declined over time (P = .0006 and P < .0001).., Conclusions: VCE adverse event rates were generally low, and retention and small bowel incomplete examination rates declined over the past two decades. Patients with known inflammatory bowel disease or elder should be alerted to high risk of retention or small bowel incomplete examination (PROSPERO: CRD42019139595).