Alpha 2-adrenoceptor participates in anti-hyperalgesia by regulating metabolic demand.

The α2-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the α2-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, α2-adrenoceptor mRNA expression was significantly upregulated, and α2-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular-mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25 h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the α2-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.

MdPRX34L, a class III peroxidase gene, activates the immune response in apple to the fungal pathogen Botryosphaeria dothidea.

MAIN CONCLUSION: MdPRX34L enhanced resistance to Botryosphaeria dothidea by increasing salicylic acid (SA) and abscisic acid (ABA) content as well as the expression of related defense genes. The class III peroxidase (PRX) multigene family is involved in complex biological processes. However, the molecular mechanism of PRXs in the pathogen defense of plants against Botryosphaeria dothidea (B. dothidea) remains unclear. Here, we cloned the PRX gene MdPRX34L, which was identified as a positive regulator of the defense response to B. dothidea, from the apple cultivar 'Royal Gala.' Overexpression of MdPRX34L in apple calli decreased sensitivity to salicylic acid (SA) and abscisic acid（ABA). Subsequently, overexpression of MdPRX34L in apple calli increased resistance to B. dothidea infection. In addition, SA contents and the expression levels of genes related to SA synthesis and signaling in apple calli overexpressing MdPRX34L were higher than those in the control after inoculation, suggesting that MdPRX34L enhances resistance to B. dothidea via the SA pathway. Interestingly, infections in apple calli by B. dothidea caused an increase in endogenous levels of ABA followed by induction of ABA-related genes expression. These findings suggest a potential mechanism by which MdPRX34L enhances plant-pathogen defense against B. dothidea by regulating the SA and ABA pathways.

Tailored Exfoliation of Polymeric Carbon Nitride for Photocatalytic H2O2 Production and CH4 Valorization Mediated by O2 Activation.

The exfoliation of bulk C3N4 (BCN) into ultrathin layered structure is an effective strategy to boost photocatalytic efficiency by exposing interior active sites and accelerating charge separation and transportation. Herein, we report a novel nitrate anion intercalation-decomposition (NID) strategy that is effective in peeling off BCN into few-layer C3N4 (fl-CN) with tailored thickness down to bi-layer. This strategy only involves hydrothermal treatment of BCN in diluted HNO3 aqueous solution, followed by pyrolysis at various temperatures. The decomposition of the nitrate anions not only exfoliates BCN and changes the band structure, but also incorporates oxygen species onto fl-CN, which is conducive to O2 adsorption and hence relevant chemical processes. In photocatalytic O2 reduction under visible light irradiation, the H2O2 production rate over the optimal fl-CN-530 catalyst is 952 µmol g-1 h-1, which is 8.8 times that over BCN. More importantly, under full arc irradiation and in the absence of hole scavenger, CH4 can be photocatalytically oxidized by on-site formed H2O2 and active oxygen species to generate value-added C1 oxygenates with high selectivity of 99.2 % and record-high production rate of 1893 µmol g-1 h-1 among the metal-free C3N4-based photocatalysts.

Registered trials on novel therapies for myasthenia gravis: a cross-sectional study on ClinicalTrials.gov.

Novel biologics in MG therapy research is on the rise. This research aimed to investigate the characteristics of registered trials on novel therapies for myasthenia gravis on ClinicalTrials.gov. This cross-sectional study used a descriptive approach to assess the features of the included trials on ClinicalTrials.gov. We found 62 registered trials from 2007 to 2023 on ClinicalTrials.gov. The results showed a yearly rise in the number of registered trials (r = 0.76, p < 0.001). Following 2017, more industry-sponsored trials were conducted (91.5% [43] vs. 60% [9], p = 0.009), fewer results were released (10.6% [5] vs. 60% [9], p = 0.001), and more trials entered phase 3 (67.4% [31] vs. 20% [2], p = 0.001). The most researched novel medications were neonatal Fc receptor inhibitors (51.2% [21]), complement inhibitors (39.0% [16]), and B cell depletors (14.6% [6]). According to the website's data, the neonatal Fc receptor inhibitors and complement inhibitors were effective in treating myasthenia gravis patients in three trials (NCT03315130, NCT03669588, and NCT00727194). This study provides valuable insights into the profile of registered trials on novel therapies for myasthenia gravis. More clinical studies are needed in the future to prove the value of its application.

ortho-Cyanomethylation of aryl fluoroalkyl sulfoxides via a sulfonium-Claisen rearrangement.

We hereby report the ortho-cyanomethylation of aryl fluoroalkyl sulfoxides with acetonitrile through a sulfonium-Claisen-type rearrangement. This reaction enables the incorporation of two valuable functional groups, such as the cyanomethyl group and the fluoroalkylthio group, into arenes. Remarkably, fluoroalkylthio groups, such as SCFH2 and SCF2H, bearing active hydrogen, are well tolerated by the reaction. The success of the reaction relies on the use of an excess amount of acetonitrile and the electronegative effect of fluoroalkyl substituents, both of which promote the electrophilic assembly of sulfoxides with acetonitrile. Consequently, the sulfonium-Claisen rearrangement reaction tolerates a wide variety of fluoroalkyl sulfoxides bearing functional groups including halides, nitriles, ketones, sulfones, and amides, which are appealing for subsequent elaboration and exploration.

Alleviating sample imbalance in water quality assessment using the VAE-WGAN-GP model.

Water resources are essential for sustaining human life and promoting sustainable development. However, rapid urbanization and industrialization have resulted in a decline in freshwater availability. Effective prevention and control of water pollution are essential for ecological balance and human well-being. Water quality assessment is crucial for monitoring and managing water resources. Existing machine learning-based assessment methods tend to classify the results into the majority class, leading to inaccuracies in the outcomes due to the prevalent issue of imbalanced class sample distribution in practical scenarios. To tackle the issue, we propose a novel approach that utilizes the VAE-WGAN-GP model. The VAE-WGAN-GP model combines the encoding and decoding mechanisms of VAE with the adversarial learning of GAN. It generates synthetic samples that closely resemble real samples, effectively compensating data of the scarcity category in water quality evaluation. Our contributions include (1) introducing a deep generative model to alleviate the issue of imbalanced category samples in water quality assessment, (2) demonstrating the faster convergence speed and improved potential distribution learning ability of the proposed VAE-WGAN-GP model, (3) introducing the compensation degree concept and conducting comprehensive compensation experiments, resulting in a 9.7% increase in the accuracy of water quality assessment for multi-classification imbalance samples.

Quantification and antibiotic resistance risk assessment of chlorination-residual viable/VBNC Escherichia coli and Enterococcus in on-site hospital wastewater treatment system.

On-site hospital wastewater treatment system widely applying chlorination has been regarded as an important barrier to curb the dissemination of antibiotic resistance. Chlorination-residual viable and viable but non-culturable (VBNC) bacteria probably lead to overestimate the effect of disinfection, while their antibiotic resistance risks imported from hospital effluents to municipal pipe network may be ignored. In this study, we quantified viable/VBNC Escherichia coli and Enterococcus in chlorination of an on-site hospital wastewater treatment system and assessed their antibiotic resistance risks. The numbers of viable/VBNC Escherichia coli and Enterococcus in raw wastewater were detected as high as 5.76-6.34/5.76-6.33 and 5.44-5.76/5.44-5.75 log10(cells/mL). Meanwhile, high proportions of antibiotic-resistant Escherichia coli and Enterococcus to culturable Escherichia coli and Enterococcus were observed, especially carrying ampicillin resistance (22.25-41.70 % and 28.09-54.05 %). Chlorination could remove 0.44-1.88-/0.43-1.88- and 0.29-1.29-/0.28-1.28-log of viable/VBNC and complete culturable Escherichia coli and Enterococcus, but cause antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) to be released outside cells, and possibly further enhance the antibiotic resistance of viable bacteria. Low detections of antibiotics suggested that the occurrence of antibiotic-resistant bacteria (ARB) may not be accompanied by the corresponding antibiotics. Different sampling months had some impacts on above results, while the results were basically stable at different sampling times of hospital daily working period. The high release rates (11.26-13.02 and 11.59-12.98 log10(cells/h)) and cumulative amounts (15.41-16.12 and 15.75-16.14 log10(cells)) of chlorination-residual viable/VBNC Escherichia coli and Enterococcus indirectly assessed the potential risks of bacterial antibiotic resistance entering municipal pipe network. Additionally, the contributions from the corresponding antibiotic ceftazidime, ciprofloxacin, and vancomycin with the cumulative amounts of 2.57-4.85, 5.73-7.50, and 5.21-7.14 kg should also be taken seriously. Residual chlorine could serve as an important signal indicator for the risk assessment.

Effect of yeast culture supplementation on blood characteristics, body development, intestinal morphology, and enzyme activities in geese.

The objective of this experiment is to evaluate the effects of yeast culture (YC) supplementation on blood characteristics, body size, carcass characteristics, organ weights, intestinal morphology, and enzyme activities. Five groups of geese were randomly assigned to five dietary treatments: the basal diet (control) and basal diets plus 0.5%, 1.0%, 2.0%, or 4.0% YC. Compared with the controls, YC supplementation at 0.5% and 1.0% increased the serum total protein (TP), albumin (ALB), and globulin (GLO) and decreased the uric acid and creatine kinase (CK) contents (p < 0.05). YC supplementation at 2.0% and 4.0% increased the CK, growth hormone, catalase and glutathione reductase contents, and relative proventriculus weights, and decreased the TP, ALB, and GLO contents, relative liver, gizzard, jejunum, ileum, and thymus weights (p < 0.05). YC supplementation at 2.0% improved fossil bone length, breast muscle percentage, jejunal villus height, ileal and jejunal villus height/crypt depth ratios, pepsin, lipase, amylase and pancreatic trypsin activities, and decreased abdominal fat percentage (p < 0.05). Furthermore, YC inclusion increased the body slope length (linear, p = 0.002; quadratic, p = 0.02), breast width (quadratic, p = 0.02), ileal (linear, p = 0.04; quadratic, p = 0.01) and duodenal villus height (cubic, p = 0.04), and decreased the relative gizzard (quadratic, p = 0.04) and thymus (linear, p = 0.002; quadratic, p = 0.02; cubic, p = 0.02) weights, liver (linear, p = 0.002; quadratic, p = 0.02), and serum (linear, p = 0.006; quadratic, p = 0.03) malondialdehyde contents, and jejunal crypt depth (quadratic, p = 0.03). The findings indicated that the YC supplementation had a positive effect on the growth and development of geese, with 2% YC being the most effective.

Uncovering novel disinfection mechanisms of solar light/periodate system: The dominance of singlet oxygen and metabolomic insights.

Disinfection plays an essential role in waterborne pathogen control and disease prevention, especially during the COVID-19 pandemic. Catalyst-free solar light/periodate (PI) system has recently presented great potential in water disinfection, whereas the in-depth chemical and microbiological mechanisms for efficient bacterial inactivation remain unclear. Our work delineated firstly the critical role of singlet oxygen, instead of reported hydroxyl radicals and superoxide radicals, in dominating bacterial inactivation by the PI/simulated sunlight (SSL) system. Multi-evidence demonstrated the prominent disinfection performance of this system for Staphylococcus aureus in terms of culturability (> 6 logs CFU), cellular integrity, and metabolic activity. Particularly, the excellent intracellular DNA removal (> 95%) indicated that PI/SSL system may function as a selective disinfection strategy to diminish bacterial culturability without damaging the cell membrane. The PI/SSL system could also effectively inhibit bacterial regrowth for > 5 days and horizontal gene transfer between E. coli genera. Nontargeted metabolomic analysis suggested that PI/SSL system inactivated bacteria by triggering the accumulation of intracellular reactive oxygen species and the depletion of reduced glutathione. Additionally, the PI/SSL system could accomplish simultaneous micropollutant removal and bacterial inactivation, suggesting its versatility in water decontamination. Overall, this study deciphers more comprehensive antibacterial mechanisms of this environmentally friendly disinfection system, facilitating the technical development and application of the selective disinfection strategy in environmental pathogen control.

Genome-wide evolutionary analysis of AUX/IAA gene family in wheat identifies a novel gene TaIAA15-1A regulating flowering time by interacting with ARF.

Flowering time is a critical agronomic trait that has strong effects on crop yields. Auxin signaling pathway plays an important role in various development processes, such as flowering, grain development. However, no Aux/IAA gene had been reported to have functions involving in wheat flowering time. Here, we systematically performed genome-wide identification, classification, domain distribution, exon-intron structure, chromosome locations and global expression pattern of Aux/IAA gene family in 14 plant genomes (including Triticum aestivum). A phylogenetic model was proposed to infer the Aux/IAA evolutionary history involving in a central exon-intron structure "2121" during evolution. Overexpression of TaIAA15-1A caused an early flowering time in Brachypodium. RNA-seq analysis showed that TaIAA15-1A overexpression alters various pathways including phytohormone signaling pathway, flowering-related pathway, and polyamine biosynthesis pathway. Screening of auxin response factor (ARF) genes identified BdARF16 that interacted with TaIAA15-1A. Exogenous polyamine (spermidine and spermine) treatments promoted early flowering and (putrescine and DCHA) delayed flowering time of WT plants. Our finding will provide insights on mechanisms of Aux/IAAs gene family and TaIAA15-1A, illustrating the potential during crop improvement programs.

The Aux/IAA protein TaIAA15-1A confers drought tolerance in Brachypodium by regulating abscisic acid signal pathway.

KEY MESSAGE: Overexpression of the Aux/IAA protein TaIAA15-1A from wheat improves drought tolerance by regulating the ABA signalling pathway in transgenic Brachypodium. Drought is a major abiotic stress that causes severe crop yield loss. Aux/IAA genes have been shown to be involved in drought stress responses. However, to the best of our knowledge, there has been little research on the molecular mechanism of the wheat Aux/IAA gene in the context of drought tolerance. In this study, we found that expression of the wheat Aux/IAA gene TaIAA15-1A was upregulated by PEG6000, NaCl, SA, JA, IAA and ABA. Transgenic plants overexpressing TaIAA15-1A showed higher drought tolerance than wild-type (WT) plants. The physiological analyses showed that the transgenic lines exhibited a higher survival rate, shoot length, and relative water content than the WT plants. The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were enhanced in transgenic lines, causing a reduction in the hydrogen peroxide (H2O2) and superoxide anion radical (O2-) contents. Transcriptome analysis showed that TaIAA15-1A overexpression alters the expression of these genes involved in the auxin signalling pathway, ABA signalling pathway, phenolamides and antioxidant pathways. The results of exogenous ABA treatment suggested that TaIAA15-1A overexpression increased sensitivity to ABA at the germination and postgermination stages compared to WT plants. These results indicate that TaIAA15-1A plays a positive role in plant drought tolerance by regulating ABA-related genes and improving antioxidative stress ability and has potential application in genetically modified crops.

The association between parent-child relationship and problematic internet use among English- and Chinese-language studies: A meta-analysis.

As past studies of the association between parent-child relationship and problematic internet use show mixed results and are influenced by many factors, this meta-analysis of 75 primary Chinese and English language studies from 1990 to 2021 with 110,601 participants (aged 6-25 years) explored (a) the overall association between parent-child relationship and problematic internet use, and (b) whether the association is affected by their types, country, measures, objects of the parent-child relationship, gender, age, year and publication types. We used funnel plots, Classic fail-safe N and Egger's test to test for publication bias and for moderation with the homogeneity tests. The results showed a negative association between quality of parent-child relationship and problematic internet use (r = -0.18, 95% CI = [-0.20, -0.15]). The moderation analysis found that compared with internet addiction tendency, the association between social media addiction and parent-child relationship was stronger. Moreover, the association between the parent-child relationship and problematic internet use of emerging adults (18-25 years old) was stronger than that of adolescents (12-18 years old). Furthermore, the negative association between parent-child relationship and problematic internet use was weaker (a) in Italy than those in Turkey and China, (b) when using CPS (Closeness to Parents Scale), IPPA (Inventory of Parent and Peer Attachment), or PARQ (Parent-Child Relationship Questionnaire) measuring parent-child relationship than using PCCS (Parent-Child Communication Scale), (c) when using IAT measuring problematic internet use rather than using IGDS or APIUS. Hence, these results indicate a negative association between parent-child relationships and problematic internet use, and the association is moderated by types of problematic internet use, age, country, scales of both parent-child relationship and problematic internet use.

Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways.

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1ß, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.

Thermo-catalytic conversion of waste plastics into surrogate fuels over spherical activated carbon of long-life durability.

Recovery of value-added fuels or chemicals from waste plastics by pyrolysis is a promising way to eliminate the waste plastics accumulation and alleviate the energy crisis, while developing efficient catalysts of high durability remains a challenge. Herein, activated carbon spheres of various surface chemistry were fabricated and subsequently used in ex-situ catalytic pyrolysis of low-density polyethylene to produce jet fuel and gasoline-ranged hydrocarbons. Experiment results indicate that with the increase of activation time and temperature, the acidity of activated carbon increased slightly owning to the oxygen-containing functional groups increased, and the specific surface area reached the maximum value (707 m2/g) at the activation condition of 800℃ for 60 min. The enlarged specific surface area promotes the C-C bond cleavage that releases more small gases at the expense of liquid yield, and the increase in density of oxygen-containing functional groups and acidity boosts the formation of aromatic hydrocarbons in liquid. When the activated carbon spheres were activated at 800℃ for 80 min, 100% of the hydrocarbons in the liquid belonged to jet fuel and gasoline, and their selectivity was 81.70 area.% and 96.25 area.%, respectively. More importantly, the catalyst exhibits excellent catalytic activity after four reactivation cycles, where the quality of the liquid product is similar to or even better than that achieved by the fresh catalyst. Furthermore, the catalyst still showed excellent performance in the catalytic pyrolysis of waste plastic mixture.

Effects of Yeast Culture Supplementation on Growth Performance, Nutrient Digestibility, Blood Metabolites, and Immune Response in Geese.

The present study was conducted to investigate the effects of dietary yeast culture (YC) supplementation on growth performance, nutrient digestibility, blood metabolites, and immune functions in geese. One-day-old Sichuan white geese (n = 300) were randomly divided into five groups containing 0 (control), 0.5%, 1.0%, 2.0%, and 4.0% of YC in the diet for 70 days. In general, the dietary supplementation of YC significantly increased the average daily gain and feed conversion ratio (p < 0.05) in which the 1.0% or 2.0% levels were better and significantly reduced the average daily feed intake at the 2.0% level (p < 0.05). YC supplementation increased digestibility of P (quadratic, p = 0.01) and gross energy (quadratic, p = 0.04) from days 23 to 27 and crude protein from days 23 to 27 and days 64 to 68 (quadratic, p ≤ 0.05), with the 2.0% level being the most effective. Serum metabolites were significantly affected by dietary YC (p < 0.05). Supplemental YC increased IL-2 on day 28 (linear, p = 0.01; quadratic, p = 0.04) and lysozyme on day 70 (quadratic, p = 0.04) and decreased complement C4 on day 70 (linear, p = 0.05). Interferon-γ, interleukin-2, and tumor necrosis factor-α genes were mostly up-regulated after YC supplementation, and interferon-γ and interleukin-2 gene expression levels were significantly increased at the 2.0% level (p < 0.05). Taken together, dietary YC supplementation improved growth performance and affected nutrient digestibility, serum metabolites, and immune function in geese, which was optimized at the 2% YC level in the present study.

Impact of Maternal Age on Singleton Birthweight in Frozen Embryo Transfer Cycles.

Background: Previous studies have investigated the effect of maternal age on assisted reproductive technology success rates. However, little is known about the relationship between maternal age and neonatal birthweight in frozen embryo transfer (FET) cycles. Whether maternal age influences singleton birthweight in FET cycles remains to be elucidated. Methods: This study was conducted at a tertiary care center, involving singleton live births born to women undergoing frozen-thawed embryo transfer during the period from January 2010 to December 2017. A total of 12,565 women who fulfilled the inclusion criteria were enrolled and grouped into four groups according to the maternal age: <30, 30-34, 35-39, and ≥40 years old. A multivariable linear regression analysis was conducted to reveal the relationship between maternal age and neonatal birthweight with controlling for a number of potential confounders. Results: The highest proportions of low birthweight (LBW, 4.1%), high birthweight (1.2%), preterm birth (PTB, 5.9%), and very PTB (0.9%) were found in the group over 40 years old, but no significant difference was observed among the four groups. Additionally, the 35-39-year-old group had the highest rate of very LBW (0.6%), whereas the 30-34-year-old group had the lowest rate of small for gestational age (SGA, 2.7%). However, multivariate analyses revealed that neonatal outcomes including PTB, LBW, and SGA were similar between the different maternal age groups. Conclusion: Grouping with different maternal age was not associated with mean birthweight and Z-scores of singletons resulting from FET.

Higher sensitivity to Cu2+ exposure of Microcystis aeruginosa in late lag phase is beneficial to its control.

Cyanobacterial blooms are always treated in exponential phase, which demands high dosages of algicides (e.g., CuSO4). Actually, cyanobacterial blooms in late lag phase exhibit low cell-density and specific physiological/biochemical characteristics, implying the possibility of controlling blooms in a more efficient and economical way with CuSO4 treatment if cyanobacterial cells in late lag phase can be treated. In this study, the outbreakof a Microcystis bloom was simulated, and Microcystis samples in late lag and exponential phases were treated with CuSO4. The results showed that M. aeruginosa in late lag phase had a higher ratio of dividing-cells, Fv/Fm and intracellular total organic carbon content (TOC) than that in exponential phase, indicating that its metabolic activity was vigorous. M. aeruginosa in late lag phase could more easily be blocked, since a higher decrease in chlorophyll-a, Fv/Fm and membrane integrity occurred under the same dosages of CuSO4 exposure compared to M. aeruginosa in exponential phase. Meanwhile, microcystin release in late lag phase was less than that in exponential phase. Moreover, higher sensitivity in late lag phase was confirmed at the individual level, as the photosynthesis related genes psaB and rbcL were more down-regulated than those in exponential phase. In general, cyanobacteria in late lag phase exhibited higher sensitivity to CuSO4, indicating that CuSO4 treatments in late lag phase can achieve a higher control efficiency and fewer release of microcystin with low-dosages algicide. Hence, it is a more environmentally friendly strategy to control cyanobacterial blooms than the traditional strategy applied in exponential phase.

Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1ß and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.