Association of Serum Calcium with Carotid Atherosclerosis: A Meta-Analysis.

INTRODUCTION: Current studies on the association between serum calcium levels and carotid atherosclerosis have yielded inconsistent results. This study aimed to elucidate this relationship through a comprehensive meta-analysis. METHODS: A systematic search of PubMed, Embase, Cochrane Library, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Weipu (VIP), and Wanfang databases was conducted, supplemented by manual retrieval, from their inception to October 2023. Two independent researchers conducted literature searches, data extraction, and quality assessment. Meta-analysis was performed using Review Manager 5.3 software on studies that met the inclusion criteria. RESULTS: The analysis included 9 cross-sectional studies, encompassing a total sample size of 9,720 participants. The meta-analysis revealed a significant statistical difference in serum calcium levels between the carotid atherosclerosis group and the control group (p = 0.03). The standardized mean difference between the two groups was 0.21 (95% CI: 0.02, 0.41) using the control group as a reference. CONCLUSIONS: Our systematic analysis indicates a significant positive correlation between serum calcium levels and carotid atherosclerosis.

Platelets fine-tune effector responses of naïve CD4+ T cells via platelet factor 4-regulated transforming growth factor ß signaling.

BACKGROUND AND AIM: Platelets are an able regulator of CD4+ T cell immunity. Herein, the mechanisms underlying platelet-regulated effector responses of naïve CD4+ T (Tn) cells were investigated. METHODS: Platelet-Tn cell co-cultures of human cells, genetically modified murine models, and high-throughput bioinformatic analyses were combined to elucidate molecular mechanisms of platelet-dependent regulation. RESULTS: Platelets exerted sophisticated regulation on effector responses of type 1, 2, and 17 T helper (Th1/Th2/Th17) and regulatory T (Treg) cells, in time-, concentration-, and organ-dependent manners and with close cooperation of transforming growth factor ß (TGFß) and platelet factor 4 (PF4). PF4 at low concentrations reinforced TGFß signaling by heteromerizing with type III TGFß receptor (TGFBRIII), and subsequently enhanced TGFBRII expression and TGFß signaling. High-concentration PF4 had, however, opposite effects by directly binding to TGFBRII, blocking TGFß-TGFBRII ligation, and thus inhibiting TGFß signaling. Furthermore, platelet depletion markedly hampered Treg and Th17 responses in the spleen but not in the lymph nodes, blockade of platelet-Tn cell contact diminished platelet effects, while spleen injection of PF4-immobilized microparticles in PF4-deficient mice mimicked platelet effects, suggesting the importance of direct platelet-Tn contact and platelet-bound PF4 for the optimal regulatory effects by platelets. CONCLUSION: Platelets exert context-dependent regulations on effector responses of Tn cells via PF4-TGFß duet, suggesting new possibilities of platelet-targeted interventions of T cell immunity.

Response of growth, photosynthetic electron transfer, and chloroplast ultrastructure to different LED light combination in green onion (Allium fistulosum L.).

With the rapid development of facility agriculture, it has become popular to study the influences of different light qualities on the growth, material metabolism, and morphology of horticultural crops. Last several years, green onions cultivation models have undergone major changes, and facility cultivation has developed rapidly. To determine the impact of light quality on the green onions, we studied the parameters connected to photosynthesis, incorporating growth, and development, photosynthetic rate (Pn ), chlorophyll fluorescence, light response curve, photosynthetic electron transfer, and chloroplast ultrastructure. We roundly analyzed the influences of different LED light combination (white: W, white-blue combination 3:1:WB, white-green combination 3:1:WG, white-yellow combination 3:1:WY, and white-red combination 3:1:WR, light intensity: 500 ± 10 µmol photons m-2 s-1 ) on the photosynthetic performance of green onions. The WB light led to better results than those of the WR, WG, and WY. There were significant performance improvements in leaf area, plant height, stem thickness, relative growth rate (RGR), pigment content, photosynthetic capacity, photosynthetic electron transfer efficiency, and chloroplast ultrastructure integrity. In contrast, plants treated with WG and WY were exposed to appreciably blocked light, but they effectively formed a light protection mechanism. The results of this research not only provided insight into the response mechanism of crop photosynthesis to different light qualities, but they also provided a scientific foundation for better planting green onions.

The association between extreme temperature and pulmonary tuberculosis in Shandong Province, China, 2005-2016: a mixed method evaluation.

BACKGROUND: The effects of extreme temperature on infectious diseases are complex and far-reaching. There are few studies to access the relationship of pulmonary tuberculosis (PTB) with extreme temperature. The study aimed to identify whether there was association between extreme temperature and the reported morbidity of PTB in Shandong Province, China, from 2005 to 2016. METHODS: A generalized additive model (GAM) was firstly conducted to evaluate the relationship between daily reported incidence rate of PTB and extreme temperature events in the prefecture-level cities. Then, the effect estimates were pooled using meta-analysis at the provincial level. The fixed-effect model or random-effect model was selected based on the result of heterogeneity test. RESULTS: Among the 446,016 PTB reported cases, the majority of reported cases occurred in spring. The higher reported incidence rate areas were located in Liaocheng, Taian, Linyi and Heze. Extreme low temperature had an impact on the reported incidence of PTB in only one prefecture-level city, i.e., Binzhou (RR = 0.903, 95% CI: 0.817-0.999). While, extreme high temperature was found to have a positive effect on reported morbidity of PTB in Binzhou (RR = 0.924, 95% CI: 0.856-0.997) and Weihai (RR = 0.910, 95% CI: 0.843-0.982). Meta-analysis showed that extreme high temperature was associated with a decreased risk of PTB (RR = 0.982, 95% CI: 0.966-0.998). However, extreme low temperature was no relationship with the reported incidence of PTB. CONCLUSION: Our findings are suggested that extreme high temperature has significantly decreased the risk of PTB at the provincial levels. The findings have implications for developing strategies to response to climate change.

Analysis of spatial-temporal distribution of notifiable respiratory infectious diseases in Shandong Province, China during 2005-2014.

BACKGROUND: Little comprehensive information on overall epidemic trend of notifiable respiratory infectious diseases is available in Shandong Province, China. This study aimed to determine the spatiotemporal distribution and epidemic characteristics of notifiable respiratory infectious diseases. METHODS: Time series was firstly performed to describe the temporal distribution feature of notifiable respiratory infectious diseases during 2005-2014 in Shandong Province. GIS Natural Breaks (Jenks) was applied to divide the average annual incidence of notifiable respiratory infectious diseases into five grades. Spatial empirical Bayesian smoothed risk maps and excess risk maps were further used to investigate spatial patterns of notifiable respiratory infectious diseases. Global and local Moran's I statistics were used to measure the spatial autocorrelation. Spatial-temporal scanning was used to detect spatiotemporal clusters and identify high-risk locations. RESULTS: A total of 537,506 cases of notifiable respiratory infectious diseases were reported in Shandong Province during 2005-2014. The morbidity of notifiable respiratory infectious diseases had obvious seasonality with high morbidity in winter and spring. Local Moran's I analysis showed that there were 5, 23, 24, 4, 20, 8, 14, 10 and 7 high-risk counties determined for influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella, respectively. The spatial-temporal clustering analysis determined that the most likely cluster of influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella included 74, 66, 58, 56, 22, 64, 2, 75 and 56 counties, and the time frame was November 2009, March 2008, January 2007, February 2005, July 2007, December 2011, November 2009, June 2012 and May 2005, respectively. CONCLUSIONS: There were obvious spatiotemporal clusters of notifiable respiratory infectious diseases in Shandong during 2005-2014. More attention should be paid to the epidemiological and spatiotemporal characteristics of notifiable respiratory infectious diseases to establish new strategies for its control.

Photosynthetic characteristics and chloroplast ultrastructure of welsh onion (Allium fistulosum L.) grown under different LED wavelengths.

BACKGROUND: The optimized illumination of plants using light-emitting diodes (LEDs) is beneficial to their photosynthetic performance, and in recent years, LEDs have been widely used in horticultural facilities. However, there are significant differences in the responses of different crops to different wavelengths of light. Thus, the influence of artificial light on photosynthesis requires further investigation to provide theoretical guidelines for the light environments used in industrial crop production. In this study, we tested the effects of different LEDs (white, W; blue, B; green, G; yellow, Y; and red, R) with the same photon flux density (300 µmol/m2·s) on the growth, development, photosynthesis, chlorophyll fluorescence characteristics, leaf structure, and chloroplast ultrastructure of Welsh onion (Allium fistulosum L.) plants. RESULTS: Plants in the W and B treatments had significantly higher height, leaf area, and fresh weight than those in the other treatments. The photosynthetic pigment content and net photosynthetic rate (Pn) in the W treatment were significantly higher than those in the monochromatic light treatments, the transpiration rate (E) and stomatal conductance (Gs) were the highest in the B treatment, and the intercellular CO2 concentration (Ci) was the highest in the Y treatment. The non-photochemical quenching coefficient (NPQ) was the highest in the Y treatment, but the other chlorophyll fluorescence characteristics differed among treatments in the following order: W > B > R > G > Y. This includes the maximum photochemical efficiency of photosystem II (PSII) under dark adaptation (Fv/Fm), maximum photochemical efficiency of PSII under light adaptation (Fv'/Fm'), photochemical quenching coefficient (qP), actual photochemical efficiency (ΦPSII), and apparent electron transport rate (ETR). Finally, the leaf structure and chloroplast ultrastructure showed the most complete development in the B treatment. CONCLUSIONS: White and blue light significantly improved the photosynthetic efficiency of Welsh onions, whereas yellow light reduced the photosynthetic efficiency.

Low pH altered salt stress in antioxidant metabolism and nitrogen assimilation in ginger (Zingiber officinale) seedlings.

The effects of low pH on antioxidant metabolism and nitrogen (N) assimilation in ginger seedlings under salt stress were investigated. A two-way randomized block design was used: the main treatment consisted of two pH levels, normal and low pH (6.0 and 4.0, respectively), and the other treatment consisted of two salinity levels, 0 and 100 mmol l-1 Na+ (NaCl and Na2 SO4 ). The results showed that low pH decreased the malondialdehyde (MDA) and hydrogen peroxide contents of ginger seedling leaves under salt stress. Moreover, low pH and salt stress significantly decreased the contents of non-enzymatic antioxidants, including ascorbate (AsA) and glutathione (GSH), and increased the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR). In addition, salt stress inhibited the N assimilation process in ginger seedling leaves, but low pH improved N assimilation under salt stress. Our finding was that low pH alleviated oxidative damage and promoted N assimilation under salt stress.

A time-trend ecological study for identifying flood-sensitive infectious diseases in Guangxi, China from 2005 to 2012.

BACKGROUND: Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. METHODS: A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. RESULTS: A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0-9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072-1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976-5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721-1.901), tuberculosis (OR = 1.200, 95% CI: 1.036-1.391), influenza (OR = 2.614, 95% CI: 1.476-4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119-4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075-1.205), respectively. CONCLUSION: The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods.

Thrombopoietin receptor agonists shift the balance of Fcγ receptors toward inhibitory receptor IIb on monocytes in ITP.

Elevated expression of the activating Fcγ receptor (FcγR) I and FcγRIIa together with decreased expression of the inhibitory FcγRIIb are involved in the pathogenesis of primary immune thrombocytopenia (ITP). Thrombopoietin receptor agonists (TPO-RAs) have been used clinically for the management of ITP; however, little is known about the effect of TPO-RAs on FcγR modulation in ITP. In this prospective study, we measured the alteration in monocyte FcγR expression from 21 corticosteroid-resistant/relapsed patients with chronic ITP receiving eltrombopag therapy. Results showed that the mRNA and protein levels of FcγRIIb were significantly elevated after 6-week eltrombopag treatment. Concurrently, FcγRI and IIa levels decreased remarkably, whereas FcγRIII expression did not change. In vitro phagocytosis assays indicated that a shift in the balance of FcγR toward inhibitory FcγRIIb on monocytes was accompanied with a considerable decrease in monocyte/macrophage phagocytic capacity. The response to eltrombopag therapy in patients with ITP was associated with FcγR phenotype and functional changes of monocytes/macrophages. Moreover, the plasma transforming growth factor-ß1 (TGF-ß1) concentrations increased significantly in eltrombopag responders. Modulation of monocyte FcγR balance by TPO-RAs was also found in a murine model of ITP established by transferring splenocytes from immunized CD61 knockout mice into CD61(+) severe combined immunodeficient mice. Romiplostim administration in ITP mice significantly upregulated inhibitory FcγRII expression and downregulated activating FcγRI expression. These findings showed that recovery of platelet counts after TPO-RA treatment in ITP is associated with the restoration of FcγR balance toward the inhibitory FcγRIIb on monocytes, and suggested that thrombopoietic agents have a profound effect on immune modulation in ITP. This study is registered at ClinicalTrials.gov as #NCT01864512.

High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia.

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor ß was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.

Inactivation of Fam20b in the neural crest-derived mesenchyme of mouse causes multiple craniofacial defects.

The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans exert multiple roles, such as enriching signal molecules and regulating the binding of ligands to the corresponding receptors. A newly identified kinase - family with sequence similarity 20 member B (FAM20B) - is essential for the formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on the side chain of a serine residue in the protein. Although the GAG chains of proteoglycans are believed to be indispensable during craniofacial development, there are few reports on their exact functions in craniofacial organogenesis. In this study, by mating Wnt1-cre mice with Fam20b-floxed mice (Fam20bflox/flox), we created Wnt1-Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural crest-derived mesenchyme. The Wnt1-Cre;Fam20bflox/flox mice died immediately after birth because of complete cleft palates. In addition to cleft palate, Wnt1-Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia, microcephaly, suture widening, and reduced mineralization in the calvaria, facial bones, and temporomandibular joint. These findings indicate that the proteoglycans formed through the catalysis of FAM20B are essential for the morphogenesis and mineralization of the craniofacial complex.

Cytokine changes in response to TPO receptor agonist treatment in primary immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-ß1 (TGF-ß1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-ß1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-ß1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-ß1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-ß1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP.

Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.

Cytotoxic T-lymphocyte (CTL)-mediated platelet destruction and aberrant cytokine profiles play important roles in the pathogenesis of primary immune thrombocytopenia (ITP). Interleukin-27 (IL-27) has pleiotropic immunomodulatory effects. However, the effect of IL-27 on CTL activity in ITP has not been reported. In the present study, platelets from ITP patients were cultured with autologous CTLs in the presence of IL-27. We found that IL-27 could inhibit CTL-mediated platelet destruction. In these IL-27-treated CTLs, granzyme B and T-bet expression decreased significantly, whereas granzyme A, perforin, and eomesodermin were not affected. To further investigate the role of granzyme B in CTL-mediated platelet destruction, granzyme B inhibitor was added and platelet apoptosis was significantly inhibited. These results suggest that IL-27 negatively regulates CTL cytotoxicity toward platelets in ITP by decreasing granzyme B expression, which is associated with reduced T-bet expression. IL-27 may have a therapeutic role in treating ITP patients.

Evodiamine inhibits the proliferation of leukemia cell line K562 by regulating peroxisome proliferators-activated receptor gamma (PPARγ) pathway.

Evodiamine, a quinolone alkaloid, is one of the major bioactive compounds of Evodia rutaecarpa Bentham (Rutaceae). It exhibits excellent biological activities, especially the anticancer activity. This study aims to investigate the effect of evodiamine on the proliferation of leukemia cell line K562 and to explore the underlying mechanism. The effect of evodiamine on K562 cells proliferation was analyzed by trypan blue dye exclusion assay and MTT assay. The expression levels of peroxisome proliferators-activated receptor gamma (PPARγ), cyclin D1, and p21 were detected by western blot assay. The results demonstrated that evodiamine inhibited the proliferation and decreased the viability of K562 cells in a dose- and time-dependent manner. 2-Chloro-5-nitro-N-phenylbenzamide (GW9662) and/or PPARγ-siRNA pretreatment alleviated the cell growth suppression triggered by evodiamine. Meanwhile, evodiamine intervention elevated the expression of PPARγ in K562 cells, while pretreatment with GW9662 attenuated the enhanced upregulation of PPARγ expression induced by evodiamine. In addition, GW9662 and PPARγ-siRNA pretreatment also significantly attenuated the downregulation of the cell cycle control protein cyclin D1 and the upregulation of cyclin-dependent kinase inhibitor p21 induced by evodiamine. In conclusion, PPARγ signaling pathway may involve in the proliferation inhibition of evodiamine on K562 cells via inhibiting cylcin D1 and stimulating of p21.

Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells.

The transcriptional coactivator p300 is highly expressed in breast cancer tissues. MRTF-A is a transcription factor governed by the Rho-GTPase-actin signaling pathway. The purpose of this study was to explore the role of p300 in breast cancer metastasis. Here we showed that the motility of breast cancer cells was enhanced by the overexpression of p300, meanwhile, the transcription of migration-related genes was upregulated. Depletion of p300 downregulated the migration-related genes and slowed down the migration of breast cancer cells. p300 worked synergistically with MRTF-A to activate the transcription of MYH9, MYL9 and CYR61. As identified by co-IP, p300 interacted with the C-terminal TAD domain of MRTF-A. And together with MRTF-A, p300 was associated with the target gene promoters. Furthermore, MRTF-A was found to be acetylated in MCF-7 breast cancer cells. These results demonstrated the involvement of p300 in the MRTF-A mediated gene regulation and breast cancer cell migration.

Can the implementation of the smart city pilot policy improve the social adaptive health and mental health of middle-aged and elderly people? Evidence from China.

With the accelerating pace of population aging in China and the implementation of the smart city pilot policy, whether the middle-aged and elderly population can integrate and adapt to this "smart" society has become an urgent problem that needs to be solved. In this context, exploring the impact of smart city pilot policies on the social adaptation health and mental health of middle-aged and elderly people has become a top priority for China to implement a national strategy to actively respond to population aging. Thus, based on panel data from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011, 2013, and 2015, this study employs the difference-in-differences (DID) method to investigate whether the smart city pilot policy can improve the social adaptive health and mental health of middle-aged and elderly people and to explore in depth the mechanism of its influence. The study finds that compared with non-pilot cities, the social adaptive health and mental health of middle-aged and elderly people in smart cities improve by 0.6% and 2.2%, respectively. The mechanism effect study shows that the smart city pilot policy can improve the mental health of the middle-aged and the elderly through the use of Information and Communication Technology (ICT) and the enhancement of human capital. Furthermore, for the social adaptive health of middle-aged and elderly individuals, the smart city pilot policy can only make improvements through the enhancement of human capital. Heterogeneity analysis shows that the effect of smart city pilot policies on social adaptive health is more pronounced in the middle-aged group than in the elderly group.

Effect of ofloxacin levels on growth, photosynthesis and chlorophyll fluorescence kinetics in tomato.

Antibiotic pollution has become a global environmental pollution problem. Chlorophyll fluorescence is one of the most important indicators reflecting the degree to which plants are influenced by the environment. Ofloxacin (OFL) is a highly toxic antibiotic pollutant, and there are few reports on the effects of changes in OFL levels on tomato chlorophyll fluorescence parameters. In this study, we investigated the responses of tomato growth, photosynthetic activity and chlorophyll fluorescence kinetics to exogenous OFL exposure (as the concentrations of 0, 2.5, 5, 10 and 20 mg L-1). The results showed that lower concentrations of OFL (2.5 mg L-1) had little impact on tomato growth, while plant growth was inhibited with the OFL concentration increasing. At higher OFL concentrations (5, 10 and 20 mg L-1), chloroplasts ruptured, and chlorophyll became degraded, resulting in leaf etiolation. Furthermore, the photosynthetic and photochemical efficiency and electron transfer rate were significantly inhibited by OFL. Moreover, damage to the oxygen-evolving complex on the donor side of PSⅡ prevented electron transfer from QA to QB and led to photoinhibition. In conclusion, higher OFL concentration reduced photosynthesis by destroying the photosynthetic mechanism in tomato, resulting in tomato leaf etiolation and plant growth inhibition.

The Chemokines Initiating and Maintaining Immune Hot Phenotype Are Prognostic in ICB of HNSCC.

Background: The immune checkpoint blockade (ICB) with anti-programmed cell death protein 1(PD-1) on HNSCC is not as effective as on other tumors. In this study, we try to find out the key factors in the heterogeneous tumor-associated monocyte/macrophage (TAMM) that could regulate immune responses and predict the validity of ICB on HNSCC. Experimental Design: To explore the correlation of the TAMM heterogeneity with the immune properties and prognosis of HNSCC, we established the differentiation trajectory of TAMM by analyzing the single-cell RNA-seq data of HNSCC, by which the HNSCC patients were divided into different sub-populations. Then, we exploited the topology of the network to screen out the genes critical for immune hot phenotype of HNSCC, as well as their roles in TAMM differentiation, tumor immune cycle, and progression. Finally, these key genes were used to construct a neural net model via deep-learning framework to predict the validity of treatment with anti-PD-1/PDL-1 Results: According to the differentiation trajectory, the genes involved in TAMM differentiation were categorized into early and later groups. Then, the early group genes divided the HNSCC patients into sub-populations with more detailed immune properties. Through network topology, CXCL9, 10, 11, and CLL5 related to TAMM differentiation in the TME were identified as the key genes initiating and maintaining the immune hot phenotype in HNSCC by remarkably strengthening immune responses and infiltration. Genome wide, CASP8 mutations were found to be key to triggering immune responses in the immune hot phenotype. On the other hand, in the immune cold phenotype, the evident changes in CNV resulted in immune evasion by disrupting immune balance. Finally, based on the framework of CXCL9-11, CLL5, CD8+, CD4+ T cells, and Macrophage M1, the neural network model could predict the validity of PD-1/PDL-1 therapy with 75% of AUC in the test cohort. Conclusion: We concluded that the CXCL9, 10,11, and CCL5 mediated TAMM differentiation and constructed immune hot phenotype of HNSCC. Since they positively regulated immune cells and immune cycle in HNSCC, the CXCL9-11 and CCL5 could be used to predict the effects of anti-PD-1/PDL-1 therapy on HNSCC.

Ofloxacin induces etiolation in Welsh onion leaves.

Antibiotic pollution has become an important global issue, and ofloxacin (OFL) is widely used worldwide. However, little is known about the potential adverse effects of OFL on plants. We assessed the toxic effects of OFL on Welsh onion and explored its toxicity mechanism. The leaf pigment content increased in 0.1 mg/L of OFL but decreased in a dose-dependent manner (0.5-2 mg/L OFL) until leaf etiolation. The ultrastructure of leaves showed that the treatment of 2 mg/L OFL produced significant toxicity. Furthermore, photosynthetic and fluorescence parameters were negatively affected by OFL treatment. The photosynthetic electron transport chain was significantly inhibited by OFL treatment, especially between QA and QB. The hydrogen peroxide and malondialdehyde content also increased with OFL concentration, indicating that antioxidant enzymes' role in antibiotic response is limited. In conclusion, OFL can damage chloroplasts by promoting ROS accumulation, which results in the etiolation of Welsh onion leaves.

Grafting resulting in alleviating tomato plant oxidative damage caused by high levels of ofloxacin.

Antibiotic pollution has become a global problem threatening human health. Ofloxacin is one of the more widely used antibiotics, but reports on the reaction of plant to ofloxacin pollution are limited. In this study, using adversity-resistant (R), adversity-sensitive (S) and grafted plant S/R as models, we investigated the biological response of tomato to exogenous ofloxacin residues. The results showed that lower levels of ofloxacin treatment (5 mg L-1 and 10 mg L-1) promoted tomato growth, and 10 mg L-1 ofloxacin was the critical dose to stimulate growth among the different treatments. In addition, the photosynthetic and fluorescence parameters, antioxidant enzyme activities and transcription-level expression of the enzymes were stimulated by low ofloxacin treatment. However, high ofloxacin treatment (20 mg L-1 and 40 mg L-1) exhibited a significantly negative effect on plant growth, photosynthesis, fluorescence parameters, antioxidant enzyme activities and transcript levels expression. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels increased with increasing ofloxacin concentrations, indicating that the oxidative damage of plants was severe with increasing doses. In contrast, the role of antioxidant enzymes in the antibiotic response was limited at high ofloxacin concentrations. The grafting experiment demonstrated that grafted plants had the ability to alleviate ofloxacin stress. In conclusion, ofloxacin can damage the photosynthetic machinery by promoting ROS accumulation, which results in the etiolation of tomato leaves and inhibits plant growth, but grafting can reduce its.