Effect of intramuscular diazepam infusion on herpes zoster-related pain in older patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study evaluated the effectiveness, psychological effects, and sleep quality using intramuscular diazepam infusion compared with placebo in patients with herpes zoster (HZ)-related pain. METHODS: The patients were randomized to either the diazepam or control group. The diazepam group received an intramuscular injection of diazepam for 3 consecutive days, while the control group received an intramuscular injection of 0.9% normal saline. The primary outcome was pain relief on posttreatment day 4, as measured using the Visual Analog Scale (VAS). Moreover, anxiety and depression were evaluated using the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9), respectively. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 78 patients were enrolled in the trial. The mean differences in VAS scores between the two groups were 0.62 (P = 0.049) on posttreatment day 3 and 0.66 (P = 0.037) on posttreatment day 4. The effective rates of pain management in the diazepam group ranged from 10.26 to 66.67%, which were higher than those in the control group on posttreatment days 3 and 4 (P < 0.05). The mean difference in PSQI scores between the diazepam and control groups was 1.36 (P = 0.034) on posttreatment day 7. No differences were found in the incidence of analgesia-adverse 1reactions between the diazepam and placebo groups. CONCLUSIONS: The intramuscular injection of diazepam for 3 consecutive days provides effective pain management and improves the quality of life. Our study suggests that diazepam is more effective than the placebo in patients with HZ-related pain. TRIAL REGISTRATION: The study was prospectively registered at https://www.isrctn.com/trialist(Registration date: 24/01/2018; Trial ID: ISRCTN12682696).

Translocator protein alleviates allodynia and improves Schwann cell function against diabetic peripheral neuropathy via activation of the Nrf2-dependent antioxidant system and promoting autophagy.

AIMS: In diabetes, autophagy and the nuclear factor erythroid-derived-2-like 2 (Nrf2)-dependent antioxidant system are impaired. Translocator protein (TSPO) agonist Ro5-4864 alleviates neuropathic pain, including diabetic peripheral neuropathy (DPN). However, the precise mechanisms remain unclear. Thus, we investigated the effects of Ro5-4864 on autophagy and the Nrf2-dependent antioxidant system in the sciatic nerves of DPN rats. METHODS: All rats were randomly assigned to Sham or DPN group. After type 2 diabetes modelling (established by high-fat diet and streptozotocin injection) followed by behavioural tests, established DPN rats were randomly assigned to the DPN group, the Ro (TSPO agonist Ro5-4864) group, the Ro + 3-MA (autophagy inhibitor) group and the Ro + ML385 (Nrf2 inhibitor) group. Behavioural assessments were performed at baseline, on days 3, 7, 14, 21 and 28. Sciatic nerves were collected on day 28 for immunofluorescence, morphological and western blot analyses. RESULTS: Ro5-4864 alleviated allodynia and increased myelin sheath thickness and myelin protein expression after DPN. Beclin-1 (p < 0.01) and LC3-II/LC3-I ratio (p < 0.01) decreased and p62 (p < 0.01) accumulated in the DPN rats. Ro5-4864 administration increased the Beclin-1 and LC3-II/LC3-I ratio and decreased p62 accumulation. Furthermore, nuclear Nrf2 contents (p < 0.01) and cytoplasmic HO-1 (p < 0.01) and NQO1 (p < 0.01) expressions were significantly inhibited in the DPN rat, which was also improved by Ro5-4864. All the beneficial effects were abrogated by 3-MA or ML385. CONCLUSION: TSPO exhibited a potent analgesic effect and improved Schwann cell function and regeneration against DPN by activating the Nrf2-dependent antioxidant system and promoting autophagy.

The analgesic effects and neural oscillatory mechanisms of virtual reality scenes based on distraction and mindfulness strategies in human volunteers.

BACKGROUND: Virtual reality (VR) has been widely used as a non-pharmacological adjunct to pain management. However, there is no consensus on what type of VR content is the best for pain alleviation and by what means VR modulates pain perception. We used three experiments to explore the analgesic effect of VR scenes in healthy adult volunteers. METHODS: We first compared the effect of immersive VR on pain perception with active (i.e. non-immersive, two-dimensional video) and passive (i.e. no VR or audiovisual input) controls at both subjective perceptual (Experiment 1) and electrophysiological (electroencephalography) levels (Experiment 2), and then explored possible analgesic mechanisms responsible for VR scenes conveying different strategies (e.g. exploration or mindfulness; Experiment 3). RESULTS: The multisensory experience of the VR environment lowered pain intensity and unpleasantness induced by contact heat stimuli when compared with two control conditions (P=0.001 and P<0.001, respectively). The reduced pain intensity rating correlated with decreased P2 amplitude (r=0.433, P<0.001) and increased pre-stimulus spontaneous gamma oscillations (r=-0.339, P=0.004) by 32-channel electroencephalography. A VR exploration scene induced a strong sense of immersion that was associated with increased pre-stimulus gamma oscillations (r=0.529, P<0.001), whereas a VR mindfulness meditation scene had a minor effect on immersive feelings but induced strong pre-stimulus alpha oscillations (r=-0.550, P<0.001), which led to a comparable analgesic effect. CONCLUSIONS: Distinct neural mechanisms are responsible for VR-induced analgesia, deepening our understanding of the analgesic benefits of VR and its neural electrophysiological correlates. These findings support further development of digital healthcare.

Intense methane diffusive emissions in eutrophic urban lakes, Central China.

Urban lakes are hotspots of methane (CH4) emissions. Yet, actual field measurements of CH4 in these lakes are rather limited and our understanding of CH4 response to urban lake eutrophication is still incomplete. In this study, we measured dissolved CH4 concentrations and quantified CH4 diffusion from four urban lakes in subtropical China during wet and dry seasons. We found that these lakes were constantly CH4-saturated, contributing the greenhouse gas (GHG) to the atmosphere. Nutrient enrichment significantly increased CH4 concentrations and diffusive fluxes. Average CH4 flux rate in the highly-eutrophic lake zones (4.18 ± 7.68 mmol m-2 d-1) was significantly higher than those in the mesotrophic (0.19 ± 0.18 mmol m-2 d-1) and lightly/moderately-eutrophic zones (0.72 ± 2.22 mmol m-2 d-1). Seasonally, CH4 concentrations and fluxes were significantly higher in the wet season than in the dry season in the mesotrophic and the lightly/moderately-eutrophic lake zones, but an inverse pattern existed in the highly-eutrophic lake zones. CH4 concentrations and fluxes increased with elevated levels of nitrogen, phosphorus and dissolved organic carbon (DOC). The accumulation of nutrients provided autochthonous substrate for methanogenesis, indicated by a negative correlation between CH4 and the C:N ratio. Ammonium-nitrogen (NH4+-N) was the best predictor for spatial fluctuation of CH4 concentrations and diffusive fluxes in the mesotrophic and the lightly/moderately-eutrophic lake zones, while total nitrogen (TN) and total phosphorus (TP) levels showed the highest predictability in the highly-eutrophic lake zones. Based on the findings, we conclude that nutrient enrichment in urban lakes can largely increase CH4 diffusion, and that urban sewage inflow is a key concern for eutrophication boosting CH4 production and diffusive emission. Furthermore, our study reveals that small urban lakes may be an important missing source of GHG emissions in the global C accounting, and that the ratio of littoral-to-pelagic zones can be important for predicting lake-scale estimation of CH4 emission.

Determination of ß2-Agonist Residues in Fermented Ham Using UHPLC-MS/MS after Enzymatic Digestion and Sulfonic Resin Solid Phase Purification.

ß2-agonists are a class of synthetic sympathomimetic drugs with acute poisoning effects if consumed as residues in foods. To improve the efficiency of sample preparation and to overcome matrix-dependent signal suppression in the quantitative analysis of four ß2-agonists (clenbuterol, ractopamine, salbutamol, and terbutaline) residues in fermented ham, an enzyme digestion coupled cation exchange purification method for sample preparation was established using ultra-high performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). Enzymatic digests were subject to cleanup treatment on three different solid phase extraction (SPE) columns and a polymer-based strong cation resin (SCR) cartridge containing sulfonic resin was found to be optimal compared with silica-based sulfonic acid and polymer sulfonic acid resins based SPEs. The analytes were investigated over the linear range of 0.5 to 10.0 µg/kg with recovery rates of 76.0-102.0%, and a relative standard deviation of 1.8-13.3% (n = 6). The limit of detection (LOD) and the limit of quantification (LOQ) were 0.1 µg/kg and 0.3 µg/kg, respectively. This newly developed method was applied to the detection of ß2-agonist residues in 50 commercial ham products and only one sample was found to contain ß2-agonist residues (clenbuterol at 15.2 µg/kg).

Effect of sympathetic sprouting on the excitability of dorsal root ganglion neurons and afferents in a rat model of neuropathic pain.

Increased sympathetic nerve excitability has been reported to aggravate a variety of chronic pain conditions, and an increase in the number of sympathetic nerve fibers in the dorsal root ganglion (DRG) has been found in neuropathic pain (NP) models. However, the mechanism of the neurotransmitter norepinephrine (NE) released by sympathetic nerve fiber endings on the excitability of DRG neurons is still controversial, and the adrenergic receptor subtypes involved in this biological process are also controversial. In our study, we have two objectives: (1) To determine the effect of the neurotransmitter NE on the excitability of different neurons in DRG; (2) To determine which adrenergic receptors are involved in the excitability of DRG neurons by NE released by sprouting sympathetic fibers. In this experiment, a unique field potential recording method of spinal cord dorsal horn was innovatively adopted, which can be used for electrophysiological study in vivo. The results showed that： Forty days after SNI, patch clamp and field potential recording methods confirmed that NE enhanced the excitability of ipsilateral DRG large neurons, and then our in vivo electrophysiological results showed that the α2 receptor blocker Yohimbine could block the excitatory effect of NE on A-fiber and the inhibitory effect on C-fiber, while the α2A-adrenergic receptor agonist guanfacine (100 µM) had the same biological effect as NE. Finally, we concluded that NE from sympathetic fiber endings is involved in the regulation of pain signaling by acting on α2A-adrenergic receptors in DRG.

Taurine is an effective therapy against thiram induced tibial dyschondroplasia via HIF-1α/VEGFA and ß-catenin/ GSK-3ß pathways in broilers.

Thiram causes tibial dyschondroplasia in broilers, leading to a significant economic loss in the poultry industry. Our study explored the effects of taurine in thiram induced tibial dyschondroplasia (TD) through in vivo and in vitro approches. In in vivo study, thiram resulted in lameness disorder, low production parameters ALP, ACP, and a high level of NOS. While, the taurine exhibited promising effect by reducing lameness, increasing ALP, ACP levels, and significantly lowering NOS level with the restoration of the growth plate. In in vitro study, thiram caused distortion and disintegration of chondrocytes. The CCK-8 technique revealed the lower cell activity in TD as compared with the treatment group. Even, the treatment and taurine groups had higher cell activity than control group. Also, the chondrocyte morphology progressively reverted to normal after taurine treatment. It might effectively decreased the symptoms of TD in broilers and their production performance. Further research found that the taurine effectively improved chondrocytes' cell viability and recovered lameness disorder by regulation of HIF-1α, VEGFA, and Wnt/ß-catenin signaling pathways. In summary, these results indicate that taurine has a protective effect on thiram-induced broilers and it can enhance the growth activity by directly affecting the development of chondrocytes and blood vessels.

[Characterization and investigation of 16 European priority polycyclic aromatic hydrocarbons in commercial infant formula milk powder in Hangzhou].

OBJECTIVE: A gas chromatography-mass spectrometry(GC-MS) method for the determination of 16 European priority polycyclic aromatic hydrocarbons(16 EUPAHs) in infant formula milk powder was established, and the characterization and investigation of 16 EUPAHs in 70 milk formula powders were carried out in 2020. METHODS: After hydrolysis, extraction, saponification and solid phase extraction, infant formula milk powder was detected by GC-MS using DB-EUPAH capillary column(20 m×0.18 mm, 0.14 µm)and quantified by internal standard method. RESULTS: The average recoveries ranged from 67.8% to 116.2% and the relative standard deviations ranged from 2.0% to 15.1%(n=6). The limits of quantification and detection of the method were 0.5 and 0.2 µg/kg, respectively. The content of 16 EUPAHs was <0.2-0.48 µg/kg, including PAH4 content in the range of <0.2-0.91 µg/kg, the characterization and investigation of infant formula powder in 16 EUPAHs mainly chrysene, cyclopenta[c, d]pyrene, benz[a]anthracene, benzo[b]fluoranthene, benzo[g, h, i]perylene. CONCLUSION: The method is simple, accurate and suitable for the determination of 16 EUPAHs in infant formula milk powder. The result showed that the content of 16 EUPAHs in commercially available infant formula milk powder in Hangzhou was low and all of them met the limit requirement of European Union.

Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis.

BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. METHODS: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. RESULTS: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 µg/mL) and the cell viability of chondrocytes stimulated by IL-1ß was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1ß, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. CONCLUSION: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.

[Detection and content investigation of benzo[a]pyrene in infant milk powder].

OBJECTIVE: To develop a method for determination of benzo[a]pyrene and to analysis of benzo[a]pyrene content in commercially available infant milk powder. METHODS: Firstly, infant milk powder was extracted with ether-petroleum ether(1∶1, V/V) under alkaline conditions, then saponified with 1. 5 mol/L potassium hydroxide ethanol solution. After purification by solid phase extraction column, it was separated on DB-EUPAH chromatographic column(20 m×0. 18 mm×0. 14 µm) and detected by gas chromatography-mass spectrometry, and quantified using D_(12)-benzo[a]pyrene internal standard. RESULTS: When the benzo[a]pyrene in infant formula was spiked 0. 3, 1. 0, 5. 0 µg/kg, the average recoveries were 116. 7%、86. 0% and 96. 4%, respectively, and the relative standard deviations were 10. 5%、4. 2% and 4. 4%, respectively(n= 6). The limit of quantification was 0. 3 µg/kg, and the detection limit was 0. 1 µg/kg. A total of 40 domestic and imported infant milk powders sold in Hangzhou supermarkets were analyzed. The range of benzo[a]pyrene was <0. 1-0. 25 µg/kg, and the detection rate was 32. 5%. CONCLUSION: The method has the advantages of rapid operation, good purifying effect, sensitiveness and accuracy, and meets the requirements for detection of benzo[a]pyrene in infant milk powder. The investigation reveals that the benzo[a]pyrene content in the currently marketed infant milk powder is at a low level.

Translocator protein agonist Ro5-4864 alleviates neuropathic pain and promotes remyelination in the sciatic nerve.

Our previous study reported the translocator protein to play a critical role in neuropathic pain and the possible mechanisms in the spinal cord. However, its mechanism in the peripheral nervous system is poorly understood. This study was undertaken to explore the distribution of translocator protein in the dorsal root ganglion and the possible mechanisms in peripheral nervous system in a rat model of spared nerve injury. Our results showed that translocator protein was activated in dorsal root ganglion after spared nerve injury. The translocator protein signals were primarily colocalized with neurons in dorsal root ganglion. A single intrathecal (i.t.) injection of translocator protein agonist (7-chloro-5-4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiaze-pine-2) (Ro5-4864) exerted remarkable analgesic effect compared with the spared nerve injury group ( P < 0.01). After i.t. administration of 2 µg Ro5-4864 on day 3, the expression of translocator protein in ipsilateral dorsal root ganglion was significantly increased on day 7( P < 0.01) but decreased on day 14 ( P < 0.05) compared with the same point in time in the control group. The duration of translocator protein activation in dorsal root ganglion was remarkably shortened. Ro5-4864 also inhibited the activation of phospho-extracellular signal-regulated kinase 1(p-ERK1) ( P < 0.01), p-ERK2 (D7: P < 0.01, D14: P < 0.05), and brain-derived neurotrophic factor ( P < 0.05) in dorsal root ganglion. Meanwhile, i.t. administration of 2 µg Ro5-4864 on day 3 further accelerated the expression of myelin protein zero(P0) and peripheral myelin protein 22 (PMP22). Our results suggested Ro5-4864 could alleviate neuropathic pain and attenuate p-ERK and brain-derived neurotrophic factor activation in dorsal root ganglion. Furthermore, Ro5-4864 stimulated the expression of myelin regeneration proteins which may also be an important factor against neuropathic pain development. Translocator protein may present a novel target for the treatment of neuropathic pain both in the central and peripheral nervous systems.

Isotope dilution gas chromatography with mass spectrometry for the analysis of 4-octyl phenol, 4-nonylphenol, and bisphenol A in vegetable oils.

By the combination of solid-phase extraction as well as isotope dilution gas chromatography with mass spectrometry, a sensitive and reliable method for the determination of endocrine-disrupting chemicals including bisphenol A, 4-octylphenol, and 4-nonylphenol in vegetable oils was established. The application of a silica/N-(n-propyl)ethylenediamine mixed solid-phase extraction cartridge achieved relatively low matrix effects for bisphenol A, 4-octylphenol, and 4-nonylphenol in vegetable oils. Experiments were designed to evaluate the effects of derivatization, and the extraction parameters were optimized. The estimated limits of detection and quantification for bisphenol A, 4-octylphenol, and 4-nonylphenol were 0.83 and 2.5 µg/kg, respectively. In a spiked experiment in vegetable oils, the recovery of the added bisphenol A was 97.5-110.3%, recovery of the added 4-octylphenol was 64.4-87.4%, and that of 4-nonylphenol was 68.2-89.3%. This sensitive method was then applied to real vegetable oil samples from Zhejiang Province of China, and none of the target compounds were detected.

Identification of 19 phthalic acid esters in dairy products by gas chromatography with mass spectrometry.

A detection method for 19 kinds of phthalic acid ester compounds analyzed by n-hexane/ether/acetonitrile 1:7:8 v/v/v mixed solvent extraction, quick, easy, cheap, effective, rugged, and safe purification and internal standard method of quantitative gas chromatography with mass spectrometry was established. This method can effectively remove interfering materials, such as lipids, fatty acids, and pigments, from dairy products. The 19 kinds of phthalic acid ester compounds were within a 0.025-0.2 mg/kg range, the recovery rate was 65.2-125.7%, relative standard deviation was 7.9-15.4% (n = 6), and the limit of detection was 0.005-0.02 mg/kg. Concentrations of the 19 kinds of phthalic acid ester compounds ranged between 0.01 and 0.12 mg/kg in ten dairy materials and 20 dairy products. The established method is simple, rapid, accurate, and highly sensitive.

Comparative pharmacokinetics of cyclophosphamide administration alone and combination with vitamin B6 in rats.

A fast and sensitive high performance liquid chromatography coupled with mass spectrometry (LC-MS) method was developed and validated for the determination of cyclophosphamide in rat plasma with and without the combination of vitamin B6. After addition of digoxin used as the internal standard (IS), plasma samples were extracted by protein precipitation with acetonitrile (1:1, v/v), and the analytes were separated by a Kromasil C18 column (150 × 4.6 mm, 5 µm) with a mobile phase of acetonitrile-0.1% formic acid water (40:60, v/v). The detection of the analyte was monitored in positive electrospray ionization by selected ion monitoringmode. The linear range was 0.01-40 µg/mL for cyclophosphamide. The intra- and inter-day precision and accuracy were all <15%. The extraction recoveries and matrix effects of the analyte and IS were all within acceptable range. The selectivity of the method was satisfactory with no endogenous interference. The results for stabilities of cyclophosphamide and IS under various conditions were all within the acceptance criteria. The validated method was successfully applied to evaluate the drug-drug interaction of cyclophosphamide and vitamin B6 in rat plasma. The results showed no differences of pharmacokinetic behaviors between cyclophosphamide administration with and without vitamin B6.

Determination of Ethyl Carbamate in Chinese Yellow Rice Wine by Diatomaceous Earth Extraction and GC/MS Method.

A sensitive and rapid analytical method based on alkaline diatomaceous earth extraction followed by GC/MS was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC) in yellow rice wines. The optimal extraction conditions were investigated. With the application of diatomaceous earth extraction, the damage of organic acids to the capillary column was greatly reduced. By using d5-EC as an internal standard for quantitative analysis of EC, the linearity of the calibration curves was good between 10 and 1000 ng/mL. The LOD and LOQ were 1.7 and 5.0 µg/kg, respectively. The spiked level of EC was 5.0-300 µg/kg, and the average recovery of the spikes was between 78.4 and 98.2%, with an RSD between 4.3 and 8.3%. Upon validation by five laboratories when spiked with 50, 100, and 300 µg/kg, the average respective recoveries were 102.9, 102.2, and 98.7% with a RSD between 0.7 and 8.1%. The validation results demonstrated that the method is fast, simple, selective, and suitable for the determination of EC in yellow rice wines.

Simultaneous determination of ethyl carbamate and 4-(5-)methylimidazole in yellow rice wine and soy sauce by gas chromatography with mass spectrometry.

We developed a new method, based on alkaline diatomite solid-phase extraction followed by gas chromatography with mass spectrometry, for the simultaneous determination of the toxic contaminants ethyl carbamate (EC) and 4-(5-)methylimidazole (4-MEI) in yellow rice wine and soy sauce. The optimal extraction conditions were defined. With the application of alkaline diatomite solid-phase extraction, damage to the capillary column by organic acids was greatly reduced. With deuterated EC used as the internal standard, the linearity of the calibration curves for EC and 4-MEI was good with correlation coefficient above 0.99. In a spiked experiment with EC and 4-MEI in yellow rice wine and soy sauce, recovery of the added EC was 80.5-102.5% and that of 4-MEI was 78.3-92.8%. The limit of quantification and limit of detection for EC were 6.0 and 2.0 µg/kg, respectively, and for 4-MEI were 15.0 and 5.0 µg/kg, respectively. The validation results demonstrate that the method is fast, simple, and selective, and therefore is suitable for simultaneously determining the presence of EC and 4-MEI in fermented food.

Mucosal vaccines for viral diseases: Status and prospects.

Virus-associated infectious diseases are highly detrimental to human health and animal husbandry. Among all countermeasures against infectious diseases, prophylactic vaccines, which developed through traditional or novel approaches, offer potential benefits. More recently, mucosal vaccines attract attention for their extraordinary characteristics compared to conventional parenteral vaccines, particularly for mucosal-related pathogens. Representatively, coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), further accelerated the research and development efforts for mucosal vaccines by thoroughly investigating existing strategies or involving novel techniques. While several vaccine candidates achieved positive progresses, thus far, part of the current COVID-19 mucosal vaccines have shown poor performance, which underline the need for next-generation mucosal vaccines and corresponding platforms. In this review, we summarized the typical mucosal vaccines approved for humans or animals and sought to elucidate the underlying mechanisms of these successful cases. In addition, mucosal vaccines against COVID-19 that are in human clinical trials were reviewed in detail since this public health event mobilized all advanced technologies for possible solutions. Finally, the gaps in developing mucosal vaccines, potential solutions and prospects were discussed. Overall, rational application of mucosal vaccines would facilitate the establishing of mucosal immunity and block the transmission of viral diseases.

Exploration of the Active Component and Mechanisms of Shengyu Decoction Against Myelosuppression Using Network Pharmacology and in vitro Experimental Validation.

Background: Chemotherapy-induced myelosuppression (CIM) is a common adverse reaction with a high incidence rate that seriously affects human health. Shengyu Decoction (SYD) is often used to treat CIM. However, its pharmacodynamic basis and therapeutic mechanisms remain unclear. Purpose: This study aimed to clarify the active components and mechanisms of SYD in CIM. Methods: LC-QTOF/MS was used to identify the absorbable components of SYD. A series of network pharmacology methods have been applied to explore hub targets and potential mechanisms. Molecular docking was used to identify the binding ability of potential active ingredients and hub targets. Finally, in vitro experiments were performed to validate these findings. Results: In this study, 33 absorbable prototype components were identified using LC-QTOF/MS. A total of 62 possible targets of SYD in myelosuppression were identified. KEGG pathway enrichment analyses showed that some signaling pathways such as PI3K-Akt and HIF-1 may be the mechanisms by which it functions. Among them, we verified the PI3K-Akt pathway. 6 Hub proteins were screened by Protein-protein interaction (PPI) network analysis. Molecular docking results showed that four absorbable components in SYD showed good binding with six Hub targets. The effectiveness of the four predicted compounds and the mechanism were verified in vitro. It has also been shown that the active component could promote the proliferation of bone marrow stromal cells (BMSCs) and block apoptosis of BMSCs, which may be related to the PI3K-Akt pathway. This result is consistent with the network pharmacology approach and molecular docking predictions. Conclusion: Our results provided not only the candidate active component of SYD, but also a new insights into mechanism of SYD in the treatment of CIM.

Diel variability of carbon dioxide concentrations and emissions in a largest urban lake, Central China: Insights from continuous measurements.

Accurately quantifying the carbon dioxide (CO2) emissions from lakes, especially in urban areas, remains challenging due to constrained temporal resolution in field monitoring. Current lake CO2 flux estimates primarily rely on daylight measurements, yet nighttime emissions is normally overlooked. In this study, a non-dispersive infrared CO2 sensor was applied to measure dissolved CO2 concentrations over a 24-h period in a largest urban lake (Tangxun Lake) in Wuhan City, Central China, yielding extensive data on diel variability of CO2 concentrations and emissions. We showed the practicality and efficiency of the sensor for real-time continuous measurements in lakes. Our findings revealed distinct diurnal variations in CO2 concentrations (Day: 38.58 ± 23.8 µmol L-1; Night: 42.01 ± 20.2 µmol L-1) and fluxes (Day: 7.68 ± 10.34 mmol m-2 d-1; Night: 9.68 ± 9.19 mmol m-2 d-1) in the Tangxun Lake. The balance of photosynthesis and respiration is of utmost importance in modulating diurnal CO2 dynamics and can be influenced by nutrient loadings and temperature. A diel variability correction factor of 1.14 was proposed, suggesting that daytime-only measurements could underestimate CO2 emissions in urban lakes. Our data suggested that samplings between 11:00 and 12:00 could better represent the average diel CO2 fluxes. This study offered valuable insights on the diel variability of CO2 fluxes, emphasizing the importance of in situ continuous measurements to accurately quantify CO2 emissions, facilitating selections of sampling strategies and formulation of management strategies for urban lakes.

Robust and Flame-Retardant Zylon Aerogel Fibers for Wearable Thermal Insulation and Sensing in Harsh Environment.

The exceptional lightweight, highly porous, and insulating properties of aerogel fibers make them ideal for thermal insulation. However, current aerogel fibers face limitations due to their low resistance to harsh environments and a lack of intelligent responses. Herein, a universal strategy for creating polymer aerogel fibers using crosslinked nanofiber building blocks is proposed. This approach combines controlled proton absorption gelation spinning with a heat-induced crosslinking process. As a proof-of-concept, Zylon aerogel fibers that exhibited robust thermal stability (up to 650 °C), high flame retardancy (limiting oxygen index of 54.2%), and extreme chemical resistance are designed and synthesized. These fibers possess high porosity (98.6%), high breaking strength (8.6 MPa), and low thermal conductivity (0.036 W m-1 K-1 ). These aerogel fibers can be knotted or woven into textiles, utilized in harsh environments (-196-400 °C), and demonstrate sensitive self-powered sensing capabilities. This method of developing aerogel fibers expands the applications of high-performance polymer fibers and holds great potential for future applications in wearable smart protective fabrics.