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This is an article in the field of metallurgical engineering. For recycling theferrophosphorus slag which a by-products of phosphorus chemical industry,the thermodynamic calculations and experimentally investigations of the removal of SiO2 by added CaO were carried out. The results of thermodynamic calculations of the reaction between SiO2 and CaO show that: the Gibbs free energy values of generating CaO·SiO2, 2CaO·SiO2, 3CaO·SiO2 and 3CaO·2SiO2 are less than zero, when the temperature in 900～1700 K range and molar ratio of(SiO2∶CaO)= 1∶1～3. It is feasible to generate calcium silicate by adding CaO, which can be used as a method of desilicification for ferrophosphorus slag. The experimental results show that:there are two layers of the products,i.e. Ca2SiO4, Ca3SiO5in the upper layer and Fe2P in the lower layer when the pressure between 10～40 Pa and the temperature 1573 K and molar ratio of SiO2∶CaO = 1∶1. The final products were testified to be ω（Si）

Ischemic stroke poses a significant global health burden, with rapid revascularization treatments being crucial but often insufficient to mitigate ischemia-reperfusion (I/R) injury. Dexmedetomidine (DEX) has shown promise in reducing cerebral I/R injury, but its potential molecular mechanism, particularly its interaction with non-coding RNAs (ncRNAs), remains unclear. This study investigates DEX’s therapeutic effect and potential molecular mechanisms in reducing cerebral I/R injury. A transient middle cerebral artery obstruction (tMACO) model was established to simulate cerebral I/R injury in adult rats. DEX was administered pre-ischemia and post-reperfusion. RNA sequencing and bioinformatic analyses were performed on the ischemic cerebral cortex to identify differentially expressed non-coding RNAs (ncRNAs) and mRNAs. The sequencing results showed 6,494 differentially expressed (DE) mRNA and 2698 DE circRNA between the sham and tMCAO (I/R) groups. Additionally, 1809 DE lncRNA, 763 DE mRNA, and 2795 DE circRNA were identified between the I/R group and tMCAO + DEX (I/R + DEX) groups. Gene ontology (GO) analysis indicated significant enrichment in multicellular biogenesis, plasma membrane components, and protein binding. KEGG analysis further highlighted the potential mechanism of DEX action in reducing cerebral I/R injury, with hub genes involved in inflammatory pathways. This study demonstrates DEX’s efficacy in reducing cerebral I/R injury and offers insights into its brain-protective effects, especially in ischemic stroke. Further research is warranted to fully understand DEX’s neuroprotective mechanisms and its clinical applications.

Sciatica characterized by irritation, inflammation, and compression of the lower back nerve, is considered one of the most common back ailments globally. Currently, the therapeutic regimens for sciatica are experiencing a paradigm shift from the conventional pharmacological approach toward exploring potent phytochemicals from medicinal plants. There is a dire need to identify novel phytochemicals with anti-neuropathic potential. This review aimed to identify the potent phytochemicals from diverse medicinal plants capable of alleviating neuropathic pain associated with sciatica. This review describes the pathophysiology of sciatic nerve pain, its cellular mechanisms, and the pharmacological potential of various plants and phytochemicals using animal-based models of sciatic nerve injury-induced pain. Extensive searches across databases such as Medline, PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar were conducted. The findings highlights 39 families including Lamiaceae, Asteraceae, Fabaceae, and Apocyanaceae and Cucurbitaceae, effectively treating sciatic nerve injury-induced pain. Flavonoids made up 53% constituents, phenols and terpenoids made up 15%, alkaloids made up 13%, and glycosides made up 6% to be used in neuorpathic pain. Phytochemicals derived from various medicinal plants can serve as potential therapeutic targets for both acute and chronic sciatic injury-induced neuropathic pain.

Cisplatin-induced neuropathic pain poses a significant clinical challenge. This study induced neuropathy via cisplatin treatment, measuring pain levels through mechanical threshold and thermal escape latency. Isoxazolone derivatives were administered at doses of 20, 40, and 60 mg/kg to evaluate their effects on allodynia and pregabalin, a known therapeutic agent, was used for comparison. Place preference tests were conducted to gauge responses, while molecular docking and dynamic simulations assessed the binding affinity for relevant receptors. Results showed that cisplatin-induced neuropathy by day four, with reduced mechanical threshold and sustained thermal escape latency for eight days. Isoxazolone derivatives at 20 mg/kg and 40 mg/kg effectively reversed allodynia, while 60 mg/kg showed limited impact. Pregabalin exhibited similar effects, though less significance after day 10. Place preference tests demonstrated positive responses to both isoxazolone derivatives and pregabalin in allodynic rats. Molecular docking analysis highlighted strong binding to receptors, particularly cyclooxygenase-2 (Cox-2), Tumor Necrosis Factor (TNF)-α. Binding free energies indicated potent inhibitory activity of isoxazolone derivatives against Cox-2 and TNF-α. This study underscores the potential of isoxazolone derivatives as therapeutic agents for cisplatin-induced mechanical allodynia, with innovative implication for neuropathic pain treatment. Further research and validation are necessary to confirm their therapeutic efficacy and safety for human clinical use.

Ovule abortion significantly contributes to a reduction in chestnut yield. Therefore, an examination of the mechanisms underlying ovule abortion is crucial for increasing chestnut yield. In our previous study, we conducted a comprehensive multiomic analysis of fertile and abortive ovules and found that ACS genes in chestnuts (CmACS) play a crucial role in ovule development. Therefore, to further study the function of ACS genes, a total of seven CmACS members were identified, their gene structures, conserved structural domains, evolutionary trees, chromosomal localization, and promoter cis-acting elements were analyzed, and their subcellular localization was predicted and verified. The spatiotemporal specificity of the expression of the seven CmACS genes was confirmed via qRT–PCR analysis. Notably, CmACS7 was exclusively expressed in the floral organs, and its expression peaked during fertilization and decreased after fertilization. The ACC levels remained consistently greater in fertile ovules than in abortive ovules. The ACSase activity of CmACS7 was identified using the genetic transformation of chestnut healing tissue. Micro Solanum lycopersicum plants overexpressing CmACS7 had a significantly greater rate of seed failure than did wild-type plants. Our results suggest that ovule fertilization activates CmACS7 and increases ACC levels, whereas an overexpression of CmACS7 leads to an increase in ACC content in the ovule prior to fertilization, which can lead to abortion. In conclusion, the present study demonstrated that chestnut ovule abortion is caused by poor fertilization and not by nutritional competition. Optimization of the pollination and fertilization of female flowers is essential for increasing chestnut yield and reducing ovule abortion.

Abstract Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia–endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

Abstract Double-sided lapping is an precision machining method capable of obtaining high-precision surface. However, during the lapping process of thin pure copper substrate, the workpiece will be warped due to the influence of residual stress, including the machining stress and initial residual stress, which will deteriorate the flatness of the workpiece and ultimately affect the performance of components. In this study, finite element method (FEM) was adopted to study the effect of residual stress-related on the deformation of pure copper substrate during double-sided lapping. Considering the initial residual stress of the workpiece, the stress caused by the lapping and their distribution characteristics, a prediction model was proposed for simulating workpiece machining deformation in lapping process by measuring the material removal rate of the upper and lower surfaces of the workpiece under the corresponding parameters. The results showed that the primary cause of the warping deformation of the workpiece in the double-sided lapping is the redistribution of initial residual stress caused by uneven material removal on the both surfaces. The finite element simulation results were in good agreement with the experimental results.

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury. Valproate is a histone deacetylase inhibitor and multitarget drug, which has been demonstrated to protect retinal neurons. In this study, we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling. We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope. Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein, phosphorylated eukaryotic translation initiation factor 2α, and caspase-12 in the endoplasmic reticulum of retinal ganglion cells. These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress. These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Camellia oleifera Abel is rich in oil, which is beneficial to human health. Seasonal drought and uneven canopy microclimate distributions result in low yields and picking efficiencies. To reveal the features of fruit development in the canopy and evaluate the impact of pruning on the canopy microclimate and fruit parameters, a field experiment was carried out in Zhuzhou, Hunan. The C. oleifera tree canopy was divided into four positions: inside the upper canopy (UI); inside the lower canopy (LI); outside the upper canopy (UO); and outside the lower canopy (LO). A combination of high-light efficiency tree pruning and mulching with camellia shells and weedproof film (CPM) was tested and compared with mulching (M). Compared with temperature and humidity, canopy light intensity is a key climate factor that affects the development of Camellia oleifera fruits. CPM improved the canopy light distribution and increased the light intensity inside the canopy of C. oleifera. There was no significant difference in the fruit cracking rate among the four canopy positions in the CPM treatment, which indicated that the fruit maturation period tended to be consistent across the canopy positions. Treatment with CPM resulted in 24.14% and 4.11% greater yield and oil content ratios, respectively, than the treatment with M. The fresh weight of the fruits from LO was the lowest, and the fatty acid accumulation was the lowest due to the poor light availability. CMP increased fruit quality, particularly in LI, which was 41.92%, 36.36%, 13.21%, and 12.79% greater in terms of fresh weight, yield, fresh seed rate, and oil content, respectively, than M. Unfortunately, there was no discernible difference in fatty acid components between CPM and M. Our research suggested that pruning combined with the mulching of organic material is an effective way to alleviate seasonal drought and uneven fruit maturation in C. oleifera trees, further increasing yield and fruit quality.

Ovule abortion, which is the main cause of empty burs in the Chinese chestnut, affects the formation of embryos and further reduces yield; therefore, it is important to study the mechanism of ovule abortion. In this study, we analyzed the transcriptomic and metabolomic data of ovules at critical developmental stages to explore the key regulatory networks affecting ovule development. The metabolites were enriched mainly in pathways involved in phytohormone signaling, energy metabolism, and amino acid synthesis in the endoplasmic reticulum. Analysis of the differentially expressed genes (DEGs) revealed that the HSP genes were significantly down-regulated during fertilization, indicating that this process is extremely sensitive to temperature. The hormone and sucrose contents of ovules before and after fertilization and of fertile and abortive ovules at different developmental stages showed significant differences, and it is hypothesized that that abnormal temperature may disrupt hormone synthesis, affecting the synthesis and catabolism of sucrose and ultimately resulting in the abortive development of Chinese chestnut ovules. At the pollination and fertilization stage of chestnuts, spraying with ethylene, ACC, and AIB significantly increased the number of developing fruit in each prickly pod compared to CK (water) treatment. These results indicated that both ethylene and ACC increased the rate of ovule development. This study provides an important theoretical molecular basis for the subsequent regulation of ovule development and nut yield in the Chinese chestnut.

Trigeminal neuropathic pain (TNP) induces mechanical allodynia and hyperalgesia, which are known to alter gene expression in injured dorsal root ganglia primary sensory neurons. Non-coding RNAs (ncRNAs) have been linked to TNP. However, the functional mechanism underlying TNP and the expression profile of ncRNAs in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Sp5C) are still unknown. We used RNA sequencing and bioinformatics analysis to examine the TG and Sp5C transcriptomes after infraorbital nerve chronic constrictive injury (IoN-CCI). The robust changes in the gene expression of lncRNAs, circRNAs, and mRNAs were observed within the TG and Sp5C from mice that underwent IoN-CCI and the sham-operated mice (day 7). In total, 111,003 lncRNAs were found in TG and 107,157 in Sp5C; 369 lncRNAs were differentially expressed in TG, and 279 lncRNAs were differentially expressed in Sp5C. In addition, 13,216 circRNAs in TG and 21,658 circRNAs in Sp5C were identified, with 1,155 circRNAs and 2,097 circRNAs differentially expressed in TG and Sp5C, respectively. Furthermore, 5,205 DE mRNAs in TG and 3,934 DE mRNAs in Sp5C were differentially expressed between IoN-CCI and sham groups. The study revealed a high correlation of pain-related differentially expressed genes in the TG and Sp5C to anxiety, depression, inflammation, neuroinflammation, and apoptosis. Gene Ontology analysis revealed that binding-related molecular functions and membrane-related cell components were significantly enriched. Kyoto Encyclopedia of Genes and Genomes analysis shows the most significant enrichments in neurogenesis, nervous system development, neuron differentiation, adrenergic signaling, cAMP signaling, MAPK signaling, and PI3K-Akt signaling pathways. Furthermore, protein–protein interaction analysis showed that hub genes were implicated in neuropeptide signaling pathways. Functional analysis of DE ncRNA-targeting genes was mostly enriched with nociception-related signaling pathways underpinning TNP. Our findings suggest that ncRNAs are involved in TNP development and open new avenues for research and treatment.

This study introduces a steel tube slab (STS), a novel pipe-roof structure used in underground engineering, whose structural system affects the bending loading conditions during construction. However, previous study used the transverse force of the STS structure to evaluate the overall structure, which results in an unreasonable structural force and material waste. The purpose of this investigation is to analyze the longitudinal flexural performance of the STS structure through a combination of experimental and numerical investigation, and to optimize the key parameters. Firstly, by conducting three flexural experiments, the failure model, load versus displacement curves, deformation characteristics, load versus strain curves and flexural capacity are investigated. The results of laboratory tests show that there are three stages to the loading of the STS structure, including the elastic stage, the elastic-plastic stage, and the fully plastic stage, and the structure exhibits progressive ductile failure. Furthermore, the finite element software (ABAQUS) is used to establish a series of finite element models, which are verified through laboratory tests, and the parametric coupling analysis is conducted. The results show that the flange thickness, steel tube diameter and spacing between the steel tubes have significant effect on the longitudinal ultimate capacity of the STS structure, however, the bolt diameter and steel tube thickness has a limited impact. Finally, different combination parameters are analyzed using the Fuzzy mathematical theory. Subsequently, the optimum ratio of key parameters is proposed.

A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.

To facilitate the conservation of seafloor habitats and planning of offshore activities, there is a growing need for mapping marine benthos in an effective and efficient way. Acoustic data acquired by multi-beam echosounders (MBES) have been extensively used for large-scale and high-resolution seafloor characterization. A deeper understanding of the relationship between backscatter data and sediment compositions can help to identify the benthos occurrence from the MBES data. With two multi-spectral MBES datasets collected near the western Wadden Sea islands in the North Sea, we investigated the potential of mapping marine benthos through backscatter classification. Two unsupervised classification methods, i.e., Bayesian classification, which mainly exploits the backscatter strength from incident angles larger than 20°, and hierarchical clustering of the backscatter strength at different angular ranges, were employed and the results were compared. The classification results from both methods showed a good correspondence with sediment properties such as the median grain size. Moreover, based on a principal component analysis of bottom sample properties, the hierarchical clustering results indicated a better distinction between contributions from the gravel content and benthos occurrence, e.g., sand mason worm density, than Bayesian classification, through involving the backscatter angular variations. Classification for multiple frequencies, on the other hand, showed little difference regarding the relationship with bottom sample properties. Although the backscatter difference between frequencies was also found to positively correlate with certain sample properties, using multi-spectral features for acoustic classification in this study did not reveal additional information compared to single-frequency classification results.

ObjectiveThe COVID-19 pandemic has challenged the health system worldwide. This study aimed to assess how China’s hierarchical medical system (HMS) coped with COVID-19 in the short-and medium-term. We mainly measured the number and distribution of hospital visits and healthcare expenditure between primary and high-level hospitals during Beijing’s 2020–2021 pandemic relative to the 2017–2019 pre-COVID-19 benchmark period.MethodsHospital operational data were extracted from Municipal Health Statistics Information Platform. The COVID-19 period in Beijing was divided into five phases, corresponding to different characteristics, from January 2020 to October 2021. The main outcome measures in this study include the percentage change in inpatient and outpatient emergency visits, and surgeries, and changing distribution of patients between different hospital levels across Beijing’s HMS. In addition, the corresponding health expenditure in each of the 5 phases of COVID-19 was also included.ResultsIn the outbreak phase of the pandemic, the total visits of Beijing hospitals declined dramatically, where outpatient visits fell 44.6%, inpatients visits fell 47.9%; emergency visits fell 35.6%, and surgery inpatients fell 44.5%. Correspondingly, health expenditures declined 30.5% for outpatients and 43.0% for inpatients. The primary hospitals absorbed a 9.51% higher proportion of outpatients than the pre-COVID-19 level in phase 1. In phase 4, the number of patients, including non-local outpatients reached pre-pandemic 2017–2019 benchmark levels. The proportion of outpatients in primary hospitals was only 1.74% above pre-COVID-19 levels in phases 4 and 5. Health expenditure for both outpatients and inpatients reached the baseline level in phase 3 and increased nearly 10% above pre-COVID-19 levels in phases 4 and 5.ConclusionThe HMS in Beijing coped with the COVID-19 pandemic in a relatively short time, the early stage of the pandemic reflected an enhanced role for primary hospitals in the HMS, but did not permanently change patient preferences for high-level hospitals. Relative to the pre-COVID-19 benchmark, the elevated hospital expenditure in phase 4 and phase 5 pointed to hospital over-treatment or patient excess treatment demand. We suggest improving the service capacity of primary hospitals and changing the preferences of patients through health education in the post-COVID-19 world.

Jacking force is one of the important safety indicators during pipe jacking construction. Existing models for calculating jacking force are widely used in the calculation of jacking force for pipe with regular cross-sections. In this paper, considering pipe-soil interaction, the cross-sectional characteristics and the distribution characteristics between pipe and soil, the calculation equations for the jacking force of circular steel pipe with flange plate were proposed based on the pressure arch theory. The proposed equations were applied to calculate the jacking force for the Olympic Sports Center Subway Station of Line 9 in Shenyang, China, and the results were compared with the field monitoring data to predict the accurate jacking force. Based on the proposed equations, the influences of the flange plate position and steel pipe diameter on earth pressure around the pipe were analyzed. The functional relationship between the earth pressure and the position of flange plate or the pipe diameter was obtained, which provides design basis and theoretical guidance for engineering practice.

Retinal vascular diseases such as retinopathy of prematurity, diabetic retinopathy, and retinal vein occlusion, and other retinal vascular diseases, with abnormal proliferation of retinal neovascularization as the main pathological manifestation. Exosomes derived from bone marrow mesenchymal stem cells transmit biologically active molecules through paracrine action to mediate the exchange of materials and information between cells. Among them, miRNA and other contents play key roles in transmitting information to regulate the proliferation of endothelial cells, the formation of the lumen, and new blood vessels in an ischemic and hypoxic environment. And it can cross the blood-retinal barrier without causing immune and inflammatory reactions and has great potential in the treatment of ophthalmic diseases. This article summarizes the role and possible mechanism of miRNA in bone marrow mesenchymal stem cell-derived exosomes in retinal neovascularization, with a view to broadening new ideas for the application of exosomes in the diagnosis and treatment of ophthalmic diseases.

Subsurface damage (SSD) is inevitably generated during the grinding process of quartz glass. It has a great impact on sustainability, lifetime and optical performance of quartz glass components and systems. This paper proposes a non-destructive detection method for detecting SSD in ground quartz glass based on polarized laser scattering (PLS). A PLS system was built to detect SSD in ground quartz glass samples prepared with different abrasive particle sizes. The PLS detection signal value had a positive correlation with the SSD depth. The finite-difference time-domain (FDTD) method was used to simulate the laser scattering process at the SSD. The distribution of electric field intensity could reflect the location of SSD. It is concluded that the PLS system can effectively detect SSD in the ground quartz glass.

IntroductionChestnut (Castanea mollissima BL.) is an important woody grain, and its flower formation has a significant impact on fruit yield and quality. Some chestnut species in northern China re-flower in the late summer. On the one hand, the second flowering consumes a lot of nutrients in the tree, weakening the tree and thus affecting flowering in the following year. On the other hand, the number of female flowers on a single bearing branch during the second flowering is significantly higher than that of the first flowering, which can bear fruit in bunches. Therefore, these can be used to study the sex differentiation of chestnut.MethodsIn this study, the transcriptomes, metabolomes, and phytohormones of male and female chestnut flowers were determined during spring and late summer. We aimed to understand the developmental differences between the first and secondary flowering stages in chestnuts. We analysed the reasons why the number of female flowers is higher in the secondary flowering than in the first flowering and found ways to increase the number of female flowers or decrease the number of male flowers in chestnuts.ResultsTranscriptome analysis of male and female flowers in different developmental seasons revealed that EREBP-like mainly affected the development of secondary female flowers and HSP20 mainly affected the development of secondary male flowers. KEGG enrichment analysis showed that 147 common differentially-regulated genes were mainly enriched from circadian rhythm-plant, carotenoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. Metabolome analysis showed that the main differentially accumulated metabolites in female flowers were flavonoids and phenolic acids, whereas the main differentially accumulated metabolites in male flowers were lipids, flavonoids, and phenolic acids. These genes and their metabolites are positively correlated with secondary flower formation. Phytohormone analysis showed that abscisic and salicylic acids were negatively correlated with secondary flower formation. MYB305, a candidate gene for sex differentiation in chestnuts, promoted the synthesis of flavonoid substances and thus increased the number of female flowers.DiscussionWe constructed a regulatory network for secondary flower development in chestnuts, which provides a theoretical basis for the reproductive development mechanism of chestnuts. This study has important practical implications for improving chestnut yield and quality.

Neuropathic pain (NP) is the chronic pain in patients resulting from injuries or diseases in the somatosensory nervous system. However, effective treatment remains limited to opioids. Currently, there is an urgent need to develop new specific pharmaceuticals with low abuse potentiality. Cannabinoid receptor 2 (CB2R) is one of the significant receptors in the endocannabinoid system. It is widely expressed in the central nervous system, especially enriched in glial cells, and plays an important role in the occurrence and development of inflammation in the nervous system. CB2R activation has a neuroprotective effect on nerve injury. In this study, we report increased and more reactive microglia (with larger cell body, shorter processes, and fewer endpoints) observed in the spinal dorsal horn of spared nerve injury (SNI) rats. Continuous intrathecal administration of CB2R agonist PM226 attenuated mechanical and cold hyperalgesia in rats and prevented the transition of microglia to the proinflammatory stage. Thus, microglia transitioned into the neuroprotective stage. Meanwhile, the proinflammatory factors TNF-α and iNOS decreased, and the levels of anti-inflammatory factors Arg-1 and IL-10 increased. The content of P2X7 receptors in the spinal dorsal horn of rats increases with time after SNI. After continuous intrathecal administration of PM226, the content of P2X7 protein decreases significantly. The administration of P2X7 inhibitor A-438079 alleviated the mechanical hyperalgesia of rats, reduced the number of microglia, and decreased the content of P2X7. These results indicate that P2X7 is involved in the neuroprotective effect caused by CB2R activation. In conclusion, this study provides new insights into the neuroprotective mechanism of CB2R activation.

To address the inadequacies of traditional pipe-roof methods, the steel support cutting pipe method (SSCP)—a novel pipe-roof method that improves construction security and underground space usage—is proposed. To further explore the applications of SSCP, its design scheme ought to be optimized. The failure mode and mechanical behaviors of the SSCP were investigated through laboratory experiments. Subsequently, a series of finite element models (FEMs) was established to study the deformation characteristics. Further, the parameters of the steel support of the proposed structure were optimized using fuzzy mathematics. The results indicated the ultimate bearing capacity to be 366.8 kN, and the specimen began to yield when the external load reached 70% of the ultimate value. The longitudinal spacing of the steel supports, transverse steel support size, and vertical steel support size had significant effect on the vertical deformation of the steel support and the ground settlement. Finally, the optimal combination of steel supports for the SSCP structure was obtained.

Background: Because enzymes can control several metabolic pathways and regulate the production of free radicals, their simultaneous use with nanoplatforms showing protective and combinational properties is of great interest in the development of therapeutic nano-based platforms. However, enzyme immobilization on nanomaterials is not straightforward due to the toxic and unpredictable properties of nanoparticles in medical practice. Aim of review: In fact, because of the ability to load enzymes on nano-based supports and increase their renewability, scientific groups have been tempted to create potential therapeutic enzymes in this field. Therefore, this study not only pays attention to the therapeutic and diagnostic applications of diseases by enzyme–nanoparticle (NP) bio-conjugate (abbreviated as: ENB), but also considers the importance of nanoplatforms used based on their toxicity, ease of application and lack of significant adverse effects on loaded enzymes. In the following, based on the published reports, we explained that the immobilization of enzymes on polymers, inorganic metal oxide and hybrid compounds provide hopes for potential use of ENBs in medical activities. Then, the use of ENBs in bioassay activities such as paper-based or wearing biosensors and lab-on-chip/microfluidic biosensors were evaluated. Finally, this review addresses the current challenges and future perspective of ENBs in biomedical applications. Key scientific concepts of review: This literature may provide useful information regarding the application of ENBs in biosensing and therapeutic platforms.

Abstract Background To analyse the changes in curative care expenditure (CCE) associated with noncommunicable diseases (NCDs) before and after the Beijing healthcare reform, thus providing a reference for the healthcare system. Methods A total of 60 medical institutions were selected using multistage stratified cluster random sampling in Beijing, China. The records of approximately 100 million outpatients with NCDs in 2016–2018 were extracted. System of Health Accounts 2011 (SHA2011) was used to estimate the CCE. The segmented regression model was established to observe both the instant change and the slope change of intervention in interrupted time series analysis (ITSA). The study was conducted from December 2019 to May 2020 in Beijing, China. Results From SHA2011, we found that the CCE for outpatients with NCDs in Beijing were 58.59, 61.46 and 71.96 billion RMB in 2016, 2017 and 2018, respectively. The CCE continued to rise at all hospital levels, namely, tertiary, secondary, and community-level hospitals. However, the proportion of CCE in tertiary hospitals decreased. From ITSA, we can also conclude that the CCE showed a significant increasing trend change at the three hospital levels after the intervention. The drug proportion showed a significant decreasing trend change in secondary and tertiary hospitals. Conclusions Beijing healthcare reform does have an impact on the CCE of NCDs.

Abstract In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P

Abstract Background The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. Results Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. Conclusion Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer. Graphic abstract

BackgroundThe maldistributions of the health workforce showed great inconsistency when singly measured by population quantity or geographic area in China. Meanwhile, earlier studies mainly employed traditional econometric approaches to investigate determinants for the health workforce, which ignored spillover effects of influential factors on neighboring regions. Therefore, we aimed to analyze health workforce allocation in China from demographic and geographic perspectives simultaneously and then explore the spatial pattern and determinants for health workforce allocation taking account of the spillover effect.MethodsThe health resource density index (HRDI) equals the geometric mean of health resources per 1,000 persons and per square kilometer. First, the HRDI of licensed physicians (HRDI_P) and registered nurses (HRDI_N) was calculated for descriptive analysis. Then, global and local Moran's I indices were employed to explore the spatial features and aggregation clusters of the health workforce. Finally, four types of independent variables were selected: supportive resources (bed density and government health expenditure), healthcare need (proportion of the elderly population), socioeconomic factors (urbanization rate and GDP per capita), and sociocultural factors (education expenditure per pupil and park green area per capita), and then the spatial panel econometric model was used to assess direct associations and intra-region spillover effects between independent variables and HRDI_P and HRDI_N.ResultsGlobal Moran's I index of HRDI_P and HRDI_N increased from 0.2136 (P = 0.0070) to 0.2316 (P = 0.0050), and from 0.1645 (P = 0.0120) to 0.2022 (P = 0.0080), respectively. Local Moran's I suggested spatial aggregation clusters of HRDI_P and HRDI_N. For HRDI_P, bed density, government health expenditure, and GDP had significantly positive associations with local HRDI_P, while the proportion of the elderly population and education expenditure showed opposite spillover effects. More precisely, a 1% increase in the proportion of the elderly population would lead to a 0.4098% increase in HRDI_P of neighboring provinces, while a 1% increase in education expenditure leads to a 0.2688% decline in neighboring HRDI_P. For HRDI_N, the urbanization rate, bed density, and government health expenditure exerted significantly positive impacted local HRDI_N. In addition, the spillover effect was more evident in the urbanization rate, with a 1% increase in the urbanization rate relating to 0.9080% growth of HRDI_N of surrounding provinces. Negative spillover effects of education expenditure, government health expenditure, and elderly proportion were observed in neighboring HRDI_N.ConclusionThere were substantial spatial disparities in health workforce distribution in China; moreover, the health workforce showed positive spatial agglomeration with a strengthening tendency in the last decade. In addition, supportive resources, healthcare needs, and socioeconomic and sociocultural factors would affect the health labor configuration not only in a given province but also in its nearby provinces.

Macau, Hong Kong and Singapore are all facing increasing population aging. Those aged 65 and over make up the old-age population. The working-age population refers to the population aged 15 to 64. Conventionally, the burden of population aging is measured by the Old-Age Dependency Ratio, which is the ratio of the old-age population to the working-age population. As life expectancy rises, depending exclusively on age to calculate the burden of aging hinders the development of effective anti-aging strategies. The working-age population's education and the elderly's health affect the aging burden's support and generator, respectively. Including them in the calculation gives us a fuller view of the burden of aging.ObjectiveTo compare the population aging burden in Macau, Hong Kong, and Singapore by including working-age population education and elderly health.MethodsThe overall, working-age and old-age population and proportion, as well as the Old-Age Dependency Ratio of Macau, Hong Kong, and Singapore, were collected from the World Bank database. The life expectancy at 65 was extracted from the 2022 World Population Prospect. The tertiary education rate of the working-age population and the self-rated health status of the old-age population were retrieved from governments' statistical reports. We then calculated the Education-Health Adjusted Old-Age Dependency Ratio, a set of four equations showing the support of the working-age population on the old-age population, where OADRh_t and OADRuh_t represent the burden of healthy and unhealthy old-age population on the working-age population with tertiary education; similarly, OADRh_nt and OADRuh_nt indicate the burden placed on the working-age population without tertiary education by healthy and unhealthy old-age population. Lastly, for comparison with the conventional Old-Age Dependency Ratio, we generated the Weighted Education-Health Adjusted Old-Age Dependency Ratio.ResultsHong Kong has the greatest old-age population proportion and Old-Age Dependency Ratio, yet its growth rates are moderate and stable, ranging from 0 to 4% and 0 to 6%, respectively. Macau and Singapore experienced sharper changes in old-age population proportion and the Old-Age Dependency Ratio, with Macau's Old-Age Dependency Ratio varying between −2.66 and 8.50% and Singapore's ranging from −1.53 to 9.70%. Three cities showed different patterns in four Education-Health Adjusted Old-Age Dependency Ratio indicators. In Macau, the OADRh_nt and OADRuh_nt increased by 0.4 and 6.2, while the OADRh_t and OADRuh_t decreased by 13.5 and 15.3 from 2004 to 2016. In Hong Kong, only the OADRuh_t fell by 9.4, and the other three increased from 2003 to 2015. In Singapore, the OADRh_nt and OADRh_t increased by 3.8 and 1.0, while OADRuh_nt and OADRuh_t decreased by 1.2 and 3.9 from 2007 to 2011. The Weighted Education-Health Adjusted Old-Age Dependency Ratios are all smaller than the conventional Old-Age Dependency Ratio in the three regions, particularly in Singapore. The Weighted Education-Health Adjusted Old-Age Dependency Ratio of Singapore was reduced by 9.5 to 30.5% compared with the conventional Old-Age Dependency Ratio, that of Hong Kong reduced by 6.2 to 22.5%, and that of Macau reduced by 4.4 to 16.1%.ConclusionThis is the first study to compare the aging burden in Macau, Hong Kong, and Singapore in connection to working-age population education and elderly health. With the new assessment, the burden of population aging in three regions has been reduced, showing that improving the education of the working-age population and maintaining older people's wellbeing can assist authorities to deal with population aging, especially in Macau and Hong Kong.

Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund’s adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.

Gastrointestinal stromal tumors are common gastrointestinal tumors typically originating from the muscularis propria layer of the stomach. Small gastric stromal tumors are usually detected incidentally during routine endoscopic examination. Although they may have malignant potentially, controversies remain regarding the need for endoscopic resection of small gastric stromal tumors originating from the muscularis propria. According to the guidelines of the European Society of Medical Oncology, all gastrointestinal stromal tumors >2 cm in size should be resected with endoscopic surveillance recommended for tumors

Superoxide dismutase (SOD) was immobilized in zeolite imidazolate framework-8 (ZIF-8) through biomimetic mineralization method, namely SOD@ZIF-8, which was then used in the treatment of nerve damage by eliminating reactive oxygen species (ROS). A series of chemical characterization and enzymatic activity researches revealed that SOD was successfully embedded into ZIF-8 without apparent influence on the antioxidant activity of SOD. Cell level experiments showed that SOD@ZIF-8 could be effectively endocytosed by cells. The activity of SOD@ZIF-8 in scavenging ROS played a critical role in protecting SHSY-5Y cells from MPP+-induced cell model and relieving cell apoptosis, indicating that SOD@ZIF-8 could effectively rescue ROS-mediated neurological disorders though removing excessive ROS produced in vitro.

Hepatocellular carcinoma (HCC) is the main type of primary liver malignancy and the fourth leading cause of cancer-related death worldwide. MicroRNAs (miRNAs), a type of non-coding RNA that regulates gene expression mainly on post-transcriptional level has a confirmed and important role in numerous biological process. By regulating specific target genes, miRNA can act as oncogene or tumor suppressor. Recent evidence has indicated that the deregulation of miR-NAs is closely associated with the clinical pathological features of HCC. However, the precise regulatory mechanism of each miRNA and its targets in HCC has yet to be illuminated. This study demonstrates that both oncogenic and tumor suppressive miRNAs are crucial in the formation and development of HCC. miRNAs influence biological behavior including proliferation, invasion, metastasis and apoptosis by targeting critical genes. Here, we summarize current knowledge about the expression profile and function of miRNAs in HCC and discuss the potential for miRNA-based therapy for HCC.

The excavation of a foundation pit will break the original stress balance and affect the surface settlement of the natural foundation of adjacent buildings, so deformation control is very important. In this paper, numerical simulation results of the additional stress of a natural foundation caused by a foundation pit excavation were compared with experimental results to verify the accuracy of the numerical model of a foundation pit excavation and obtain a reliable ratio of building width to the average particle size of the sand that was not affected by the particle size effect. Then, the distribution and variation law of the surface settlement of a natural foundation caused by excavation was studied by a model test, and the relationship between the deformation of a natural foundation and the depth of a foundation pit excavation and the additional load of building was obtained.

Coronavirus disease (COVID-19) is an infection of the respiratory system caused by single standard RNA viruses named as Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). The disease appeared as a serious problem and the leading cause of death in human beings throughout the world. The main source of different phytochemicals are plants, which helps in the development of new drugs against various ailments. Islam is comprehensive religion and a complete code of life for Muslims. The teaching of Islam, according to the Holy Quran and Hadith are universal for the benefit of humanity. Islam believes that every ailment is from God and who made the disease definitely made its medication. There is a complete guideline with regard to taking measures against infectious diseases such as quarantine and seeking medicinal treatment. The research objective is to gather the knowledge of medicinal plants described in the Holy Quran or utilized by the Prophet (SAW) for the treatment of different ailments or advised to use them to boost immunity and strengthen the body. Scientists across the globe have found these plants beneficial for many diseases and have antiviral potential. In present study, the six plant species including Olea europaea, Nigella sativa, Allium Sativum, Allium cepa, Zingiber officinale and Cassia senna were selected which contain phytochemicals like Calcium Elenolate, Thymoquinone, S-Allylcysteine, Dipropyl Disulfide, Sesquiterpene, Monoterpene, Pelargonidin 3-Galactoside ion and Kaempferol. The phytochemicals monoterpene (from Zingiber officinale) shows best interaction with target proteins RdRP, 3CLPro, ACE2. Calcium Elonate (from olive) bonds with 3CLPro, ACE2 and Kemoferol and Pelargomidine (from Senna Makki) bonds with RdRP, ACE2. The ligands show a unique set of intersections i.e. hydrogen bonding, and alkyl interaction. These medicinal plants can be utilized immediately for the treatment of COVID-19 as their safety is already established. This treatment can enhance recovery when combined with other treatments. Furthermore, the screening of bioactive compounds or phytochemicals found in these plants can be utilized to design new therapeutic drug to treat COVID-19 pandemic.

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.

Objectives To evaluate cost-utility of universal Hepatitis B vaccination program in the Beijing city (Beijing). Methods A decision-Markov model was constructed to determine the cost-utility of the universal immunization program for infants (universal vaccination program) by comparing with a hypothetic nonvaccination strategy in Beijing. Parameters in models were extracted from Beijing Center for Disease Control and Prevention (CDC) annual work report, Beijing health statistical yearbook, National Health Survey report, Beijing 1% population sample survey report, Beijing Health and Medical Price Monitoring Data Platform, and public literatures. The incremental cost‑utility ratio (ICUR) was used to compare alternative scenarios. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess parameter uncertainties. Results The universal vaccination program had increased the utility and reduced cost among infants born in 2016 in Beijing. The ICUR was CNY −24,576.61 (US$ −3779.16) per QALY for universal vaccination program comparing with non-vaccination scenario from healthcare perspective. It was estimated that the universal vaccination would save direct medical treatment cost of CNY 2,262,869,173.50 (US$ 347,962,414.43) and prevent loss of 18322.25 QALYs within lifetime of target cohort. Discount rate accounted for the most remarkable influence on ICUR in one-way sensitivity analysis. The result of probabilistic sensitivity analysis illustrated that all of the ICURs were located in the fourth quadrant of the cost-utility incremental plot undergone 5000 times of Monte Carlo simulation. Conclusions Current universal hepatitis B vaccination program in Beijing was highly cost utility. The investment was reasonable for current universal vaccination program in Beijing.

A novel coronavirus (2019-nCov) emerged in China, at the end of December 2019 which posed an International Public Health Emergency, and later declared as a global pandemic by the World Health Organization (WHO). The International Committee on Taxonomy of Viruses (ICTV) named it SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), while the disease was named COVID-19 (Coronavirus Disease- 2019). Many questions related to the exact mode of transmission, animal origins, and antiviral therapeutics are not clear yet. Nevertheless, it is required to urgently launch a new protocol to evaluate the side effects of unapproved vaccines and antiviral therapeutics to accelerate the clinical application of new drugs. In this review, we highlight the most salient characteristics and recent findings of COVID-19 disease, molecular virology, interspecies mechanisms, and health consequences related to this disease.

Pullorum is one of the most serious diseases that endanger the chicken industry. With the advent of the era of anti-antibiotics in feed, the replacement of antibiotics by probiotics has become the focus and hotspot of related research. In this study, hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to observe the structural changes of intestinal mucosa in chicks infected with Salmonella pullorum, and to analyze TNF-α, IL-10, IFN-γ, proliferating cell nuclear antigen (PCNA), and secreted immunoglobulin A (sIgA) levels. The results showed that the intestinal villus height, villus height to crypt depth ratio (V/C), and muscle layer thickness of duodenum, jejunum and cecum in the JYBR-190 group were significantly higher than those of the infection group and antibiotic group. Furthermore, the levels of PCNA, sIgA and IL-10 in JYBR-190 group were significantly increased, whereas the expression of TNF-α and IFN-γ was significantly decreased. Taken together, Bifidobacterium lactis JYBR-190 has a protective effect on intestinal mucosal damage in chicks infected with Salmonella pullorum.

Universal stress proteins (USPs) exist across a wide range of species and are vital for survival under stressful conditions. Due to the increasingly harsh global environmental conditions, it is increasingly important to study the role of USPs in achieving stress tolerance. This review discusses the role of USPs in organisms from three aspects: (1) organisms generally have multiple USP genes that play specific roles at different developmental periods of the organism, and, due to their ubiquity, USPs can be used as an important indicator to study species evolution; (2) a comparison of the structures of USPs reveals that they generally bind ATP or its analogs at similar sequence positions, which may underlie the regulatory role of USPs; and (3) the functions of USPs in species are diverse, and are generally directly related to the stress tolerance. In microorganisms, USPs are associated with cell membrane formation, whereas in plants they may act as protein chaperones or RNA chaperones to help plants withstand stress at the molecular level and may also interact with other proteins to regulate normal plant activities. This review will provide directions for future research, focusing on USPs to provide clues for the development of stress-tolerant crop varieties and for the generation of novel green pesticide formulations in agriculture, and to better understand the evolution of drug resistance in pathogenic microorganisms in medicine.

Existing railways can no longer meet transportation requirements, and it is an urgent need to expand old tunnels. However, the existence of ventilations shaft makes expansions face greater risks. This study analyzed the tangential stress change trend during the expansion process through field monitoring, and numerical simulation was used to analyze the changes in stress and displacement under different shaft depths and width–span ratios. The results show that as one approaches the tunnel face, the tangential stress in the arch foot and side wall of the J-2 and J-3 sections gradually increased, and the tangential stress in the arch foot and side wall of the J-1 section gradually decreased. The distance of the tunnel expansion’s influence on tangential stress is about 0.91 to 1.45 times the tunnel span. The largest value of vertical displacement had a linear relationship with shaft depth, and the largest value of horizontal displacement had a quadratic relationship with shaft depth. Changes in the width–span ratio only had a greater impact on the ventilation shaft section. These results can provide a reference for similar in situ expansion projects.

Pathological retinal neovascularization (RNV) is the main character of ischemic ocular diseases, which causes severe visual impairments. Though retinal microglia are well acknowledged to play important roles in both physiological and pathological angiogenesis, the molecular mechanisms by which microglia communicates with endothelial cells (EC) remain unknown. In this study, using single-cell RNA sequencing, we revealed that the pro-inflammatory secreted protein Spp1 was the most upregulated gene in microglia in the mouse model of oxygen-induced retinopathy (OIR). Bioinformatic analysis showed that the expression of Spp1 in microglia was respectively regulated via nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor 1α (HIF-1α) pathways, which was further confirmed through in vitro assays using BV2 microglia cell line. To mimic microglia-EC communication, the bEnd.3 endothelial cell line was cultured with conditional medium (CM) from BV2. We found that adding recombinant Spp1 to bEnd.3 as well as treating with hypoxic BV2 CM significantly enhanced EC proliferation and migration, while Spp1 neutralizing blocked those CM-induced effects. Moreover, RNA sequencing of BV2 CM-treated bEnd.3 revealed a significant downregulation of Kit, one of the type III tyrosine kinase receptors that plays a critical role in cell growth and activation. We further revealed that Spp1 increased phosphorylation and expression level of Akt/mTOR signaling cascade, which might account for its pro-angiogenic effects. Finally, we showed that intravitreal injection of Spp1 neutralizing antibody attenuated pathological RNV and improved visual function. Taken together, our work suggests that Spp1 mediates microglia-EC communication in RNV via activating endothelial Kit/Akt/mTOR signaling and is a potential target to treat ischemic ocular diseases.

Coronavirus disease-2019 (COVID-19) pandemic started from Wuhan, China has infected more than 6.7 million individuals and killed more than 390,000 individuals globally. Due to the higher transmissibility and infectiousness, asymptomatic infection, and lack of effective treatment options and vaccine, fatalities and morbidities are increasing day by day globally. Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. To eradicate these risks, it is necessary to determine the COVID-19 zoonotic source of transmission to humans and clinical manifestations in infected individuals. Although, identification or development of the highly effective therapeutic agents is necessary, however, development of protective strategies against the COVID-19 by enhancing immune responses will be an asset in the current scenarios of the COVID-19 pandemic. In this paper, we discuss the transmission, health consequences, and potential management (therapeutic and preventive) options for COVID-19 disease.

Neuropathic pain is often accompanied by anxiety and depression-like manifestations. Many studies have shown that alterations in synaptic plasticity in the anterior cingulate cortex (ACC) play a critical role, but the specific underlying mechanisms remain unclear. Previously, we showed that cAMP response element-binding protein (CREB) in the dorsal root ganglion (DRG) acts as a transcription factor contributing to neuropathic pain development. At the same time, brain-derived neurotrophic factor (BDNF), as important targets of CREB, is intricate in neuronal growth, differentiation, as well as the establishment of synaptic plasticity. Here, we found that peripheral nerve injury activated the spinal cord and ACC, and silencing the ACC resulted in significant relief of pain sensitivity, anxiety, and depression in SNI rats. In parallel, the CREB/BDNF pathway was activated in the spinal cord and ACC. Central specific knockdown and peripheral non-specific inhibition of CREB reversed pain sensitivity and anxiodepression induced by peripheral nerve injury. Consequently, we identified cingulate CREB/BDNF as an assuring therapeutic method for treating neuropathic pain as well as related anxiodepression.

Rural traditional Chinese medicine hospitals bear responsibilities of providing efficient medical services for rural residents. Efficiency assessments have previously been conducted in single province. This study aimed to investigate the technical efficiency of rural traditional Chinese medicine hospitals across China from 2013 to 2018, with the application of super slack-based measure data envelopment analysis. In total, 1219 hospitals covering 28 provinces were included as sample hospitals. Overall, hospitals performed technically less efficiently but presented with an increasing trend. Redundancy and insufficiency existed in health input and output variables, respectively. Notably, optimizing input variables was found to make more substantial improvement in hospital efficiency. Provincial and regional disparities were also observed in hospital efficiency. In conclusion, rural traditional Chinese medicine hospitals have experienced slight improvement in efficiency during the study period, however, their efficiency was still in a relatively low level with ample room for improvement. Meanwhile, regional coordinated development should also be noticed in this process.

Intracerebral hemorrhage (ICH) is a serious stroke subtype with high morbidity and mortality. The prognosis of ICH is poor. In recent years, there have been many studies on how to improve the prognosis of ICH. This article mainly summarizes the research progress of ICH in translational research, including its risk factors and pathogenesis, course of disease, primary and secondary ICH brain injury, its prevention and treatment strategies.

Abstract Background Stroke is a major cause of death and disability worldwide. Over the years, traditional medicines for stroke treatment have undergone tremendous progress, but few bibliometric studies have been performed. This study explored the trends and issues relating to the application of traditional medicine in stroke research. Methods A bibliometric search was performed in the Web of Science Core Collection database to identify studies that investigated the application of traditional medicine in stroke management. CiteSpace VI and Excel 2016 were used to analyze information from the retrieved studies. Activity index and attractive index were used to explore the worldwide development modes. Results A total of 1083 English articles published between 2004 and 2018 were identified. Over the last 15 years, the developments in research occurred in three geographic clusters. The development modes were investigated and classified into 4 categories. In mainland China, the number and impact of research showed an increasing trend over the study period. The United States played a leading role in this topic. Three clusters of institutes and the majority of authors mainly came from South Korea, Taiwan and mainland China. Reperfusion injury and angiogenesis were identified as the potential topics likely to dominate future research in this field. Conclusion The progress of studies on traditional medicine for stroke could be explained by the global attention to traditional medicine, the geospatial proximity for research collabration, and the increasing resources invested. Based on a large amount of existing research, researchers engaged in this topic should objectively consider the influential studies to identify and solve the common issues worldwide.

Objectives: To assess the prevalence of hepatitis B virus (HBV) infection among married individuals and to analyze the associated risk factors of HBV infection in vaccinated and unvaccinated groups in 2006 and 2014. Methods: Information of married individuals aged over 16 y with a clear HBV vaccination status was extracted from the database constructed by the Beijing Center for Disease Prevention and Control from population-based investigation. A structured questionnaire was employed to collect demographic information, vaccinated history, and other related influence information of HBV of participants. Pearson chi-square test, Fisher's test, and logistic regression were used to explore the risk factors of HBV infection. Results: A total of 2874 individuals in 2006 and 1622 individuals in 2014 were enrolled in our study. The mean age of individuals was 49.30 and 46.68 y in 2006 and 2014, respectively. The overall positive rates of HBsAg, anti-HBc, and single anti-HBs were 4.80%, 43.01%, and 5.78% in 2006, which were 4.69%, 38.22%, and 14.18% in 2014, respectively. For vaccinated individuals, age was significantly correlated with anti-HBc in 2014 (40 < age ≤50 versus age ≤30, relative risk (RR) = 3.03, 95% confidence interval (95%CI) = 1.04–8.84). Gender [male versus female, RR = 0.60, 95%CI = 0.36–1.00 (2006); RR = 0.71, 95%CI = 0.52–0.97 (2014)] and age (in 2006) were found to be significantly associated with single anti-HBs. For unvaccinated individuals, HBsAg positivity was statistically significant correlated with gender [RR = 1.47, 95%CI = 1.04–2.06, in 2006], residence (urban versus rural, RR = 0.40, 95%CI = 0.24–0.67, in 2006; RR = 0.58, 95%CI = 0.34–0.99, in 2014), sharing syringes [RR = 3.75, 95%CI = 1.33–10.63 (in 2006); RR = 2.07, 95%CI = 1.26–3.41 (in 2014)], infected wives (RR = 1.97, 95%CI = 1.28–3.05, in 2006), and infected husbands (RR = 2.19, 95%CI = 1.25–3.82, in 2006). Anti-HBc positivity was significantly associated with gender [RR = 1.19, 95%CI = 1.10–1.30 (in 2006); RR = 1.24, 95%CI = 1.09–1.40 (in 2014)], age (in 2006 and 2014), endoscopic medicine treatment [RR = 1.16, 95%CI = 1.03–1.32 (in 2006), RR = 1.21, 95%CI = 1.01–1.45 (in 2014)], sharing syringes (RR = 1.43, 95%CI = 1.25–1.64, in 2014), body piercing (RR = 0.84, 95%CI = 0.75–0.93, in 2006), infected wives (RR = 1.32, 95%CI = 1.18–1.47, in 2006), and infected husbands (RR = 1.39, 95%CI = 1.22–1.59, in 2006). Anti-HBs positivity was associated with age (in 2006 and 2014). Conclusions: Prevalence of HBV infection was lower in 2014 than in 2006 according to HBsAg and anti-HBc positivity. Unvaccinated individuals faced much more risk of HBV infection than those of vaccinated.

The overexpression of lncRNA HOTAIR can result in cancer progression through upregulation of the Akt signaling pathway. We aimed to evaluate the anticancer effects of levan polysaccharide from Erwinia herbicola on colorectal cancer cells (HT-29) and explore the role of the ROS-mediated HOTAIR/Akt signaling pathway. The HT-29 cancer cells were treated with levan either alone or along with N-acetyl-L-cysteine (NAC), as a potential antioxidant for 24 hrs and different assays including MTT, LDH, ROS, apoptosis, SOD activity, CAT activity, caspase-3 activity, qRT-PCR, and western blot analysis were performed. It was shown that levan treatment induces apparent reduction in cell viability, SOD and CAT activity, HOTAIR expression, the ratio of pAkt protein level and a significant increase in the ROS level, apoptosis induction, and caspase-3 activity, which were effectively suppressed by NAC co-treatment. These data indicated the effective antiproliferative effect of levan on colorectal cancer cells, in which downregulation of ROS-mediated HOTAIR/Akt plays an important role.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2’s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Background: Immune checkpoint blockers (ICBs) are increasingly being used to treat patients with advanced hepatocellular carcinoma (HCC), but only a third of these patients are sensitive to ICBs. Emerging evidence suggests that ferroptosis could be a novel target for antitumor treatment, and combined treatment with ferroptosis inducers might enhance sensitivity to immunotherapy. However, there is a lack of information on the crosstalk between ferroptosis-related lncRNAs and anti-tumor immunity. Therefore, we aim to explore prognostic value of ferroptosis-related lncRNAs and clarify potential role in ICBs of HCC.Methods: We obtained mRNA and lncRNA expression data from two independent cohorts (TCGA and GEO database). Univariate Cox, the least absolute shrinkage and selection operator (Lasso) algorithm and multivariate Cox analysis were used to construct a lncRNA signature, which was evaluated using the area under the receiver operating characteristic curve (AUC) and Kaplan–Meier curves. Tumor-infiltrating cell (TIC) profiling and the tumor immune dysfunction and exclusion (TIDE) algorithm were used to validate the signature model and immunotherapy. Finally, we adopted RT-PCR assay to evaluate the differential expression of lncRNAs in HCC tissues in our hospital.Results: The ferroptosis-related lncRNA signature included five lncRNAs, most of which were positively correlated with clinical stage and grade. The signature could stratify patients into two risk groups, with the high-risk group associated with a shorter overall survival (OS, p < 0.05) in TCGA-LIHC and GSE76427. Besides, the AUCs of the 1-, 3-, and 5-years OS were 0.772, 0.707, and 0.666, respectively. Gene set enrichment analysis (GESA) of lncRNAs revealed enrichment of oncogenic and immune-related pathways. The TIC profiling indicated a close correlation between the signature and immune cells. Furthermore, the high-risk group had a better response to immunotherapy than low-risk group. RT-PCR demonstrated these five lncRNAs were upregulated in cancerous tissue than normal tissues.Conclusions: The ferroptosis-related lncRNA signature could accurately predict the OS of HCC patients and may serve as an independent clinical factor for patients’ outcomes. Ferroptosis-related lncRNAs may remodel the tumor microenvironment (TME) and affect the anti-cancer ability of ICBs, and therefore, could potentially act as an indicator for the response to immunotherapy in HCC.