Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3ß Signaling Pathway.

Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.

Strong associations between dissolved organic matter and microbial communities in the sediments of Qinghai-Tibetan Plateau lakes depend on salinity.

In aquatic ecosystems, dissolved organic matter (DOM) plays a vital role in microbial communities and the biogeochemical cycling of elements. However, little is known about the associations between DOM and microbial communities in lake sediments. This study investigated the composition of water-extractable organic matter and microbial communities in surface sediments of lakes with different salinities on the Qinghai-Tibet Plateau. Ultrahigh-resolution mass spectrometry and high-throughput microbial sequencing techniques were employed to assess the associations between molecular diversity and microbial diversity and the effects of salinity in 19 lakes spanning a salinity range from 0.22 ‰ to 341.87 ‰. Our results show that increasing salinity of lake water led to higher molecular diversity of DOM in surface sediments. High-salinity lakes exhibited distinct DOM characteristics, such as lower aromaticity, smaller molecular weight, and higher oxidation degree, compared to freshwater lakes. The complexity of the microbial network composition of sediments first increased and then decreased with the increase of salinity. Moreover, as salinity increases, the dominant species transitioned from Gammaproteobacteria to Bacteroidia, and this transition was accompanied by a decrease in microbial diversity and an increase in molecular diversity. Microbial factors accounted for 34.68 % of the variation in the molecular composition of DOM. Overall, this study emphasizes the significant effects of salinity on both molecular and microbial diversity in lake sediments. Furthermore, our findings underscore the importance of microbes in controlling the range of organic compounds present in lakes and deepen our knowledge of the biogeochemical cycling of DOM.

Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective.

Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular-glue-mediated proximity-induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC-driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC-driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure-activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer.

Report of Citrus tristeza virus in Diaphorina citri (Hemiotera: Liviidae) insects of different sexes, color morphs, and developmental stages.

Diaphorina citri, also known as the Asian citrus psyllid, is the main vector of 'Candidatus Liberibacter asiaticus' (CLas) associated with citrus Huanglongbing. It has been reported that D. citri could also be infected by Citrus tristeza virus (CTV), a virus that has been previously reported to be vectored by certain aphid species. In this study, the CTV and CLas profiles in different organs, color variants, developmental stages, or sexes of D. citri insects were analyzed. Although no significant differences were found between nymphs and adults in CTV titers, we found that the third instar nymph of D. citri was more efficient in CTV and CLas acquisition compared to the fourth and fifth instars and adults. With the instars of D. citri development, the relationship between the acquiring of CTV and CLas by D. citri seemed to follow an inverse trend, with the titer of CLas increased and the titer of CTV decreased. No significant differences were observed between the 2 sexes of D. citri in acquiring either CTV or CLas titers in the field. However, no differences were drawn among the 3 color morph variants for CTV titers. CTV titers in the midguts of adult D. citri were significantly higher than those in the salivary glands. Both CTV-positive incidence and CTV titers in the midguts of adult D. citri increased with increasing exposure periods. This study provides new data to deepen our understanding of the CTV-involved interaction between D. citri and CLas.

Drought limits vegetation carbon sequestration by affecting photosynthetic capacity of semi-arid ecosystems on the Loess Plateau.

Drought is the driver for ecosystem production in semi-arid areas. However, the response mechanism of ecosystem productivity to drought remains largely unknown. In particular, it is still unclear whether drought limits the production via photosynthetic capacity or phenological process. Herein, we assess the effects of maximum seasonal photosynthesis, growing season length, and climate on the annual gross primary productivity (GPP) in vegetation areas of the Loess Plateau using multi-source remote sensing and climate data from 2001 to 2021. We found that maximum seasonal photosynthesis rather than growing season length dominates annual GPP, with above 90 % of the study area showing significant and positive correlation. GPP and maximum seasonal photosynthesis were positively correlated with self-calibrating Palmer Drought Severity Index (scPDSI), standardized precipitation and evapotranspiration index (SPEI) in >95 % of the study area. Structural equation model demonstrated that both drought indices contributed to the annual GPP by promoting the maximum seasonal photosynthesis. Total annual precipitation had a positive and significant effect on two drought indices, whereas the effects of temperature and radiation were not significant. Evidence from wood formation data also confirmed that low precipitation inhibited long-term carbon sequestration by decreasing the maximum growth rate in forests. Our findings suggest that drought limits ecosystem carbon sequestration by inhibiting vegetation photosynthetic capacity rather than phenology, providing a support for assessing the future dynamics of the terrestrial carbon cycle and guiding landscape management in semi-arid ecosystems.

Effects of environmental microplastic exposure on Chlorella sp. biofilm characteristics and its interaction with nitric oxide signaling.

Microalgal biofilm is promising in simultaneous pollutants removal, CO2 fixation, and biomass resource transformation when wastewater is used as culturing medium. Nitric oxide (NO) often accumulates in microalgal cells under wastewater treatment relevant abiotic stresses such as nitrogen deficiency, heavy metals, and antibiotics. However, the influence of emerging contaminants such as microplastics (MPs) on microalgal intracellular NO is still unknown. Moreover, the investigated MPs concentrations among existing studies were mostly several magnitudes higher than in real wastewaters, which could offer limited guidance for the effects of MPs on microalgae at environment-relevant concentrations. Therefore, this study investigated three commonly observed MPs in wastewater at environment-relevant concentrations (10-10,000 µg/L) and explored their impacts on attached Chlorella sp. growth characteristics, nutrients removal, and anti-oxidative responses (including intracellular NO content). The nitrogen source NO3--N at 49 mg/L being 20 % of the nitrogen strength in classic BG-11 medium was selected for MPs exposure experiments because of least intracellular NO accumulation, so that disturbance of intracellular NO by nitrogen availability could be avoided. Under such condition, 10 µg/L polyethylene (PE) MPs displayed most significant microalgal growth inhibition comparing with polyvinyl chloride (PVC) and polyamide (PA) MPs, showing extraordinarily low chlorophyll a/b ratios, and highest superoxide dismutase (SOD) activity and intracellular NO content after 12 days of MPs exposure. PVC MPs exposed cultures displayed highest malonaldehyde (MDA) content because of the toxic characteristics of organochlorines, and most significant correlations of intracellular NO content with conventional anti-oxidative parameters of SOD, CAT (catalase), and MDA. MPs accelerated phosphorus removal, and the type rather than concentration of MPs displayed higher influences, following the trend of PE > PA > PVC. This study expanded the knowledge of microalgal biofilm under environment-relevant concentrations of MPs, and innovatively discovered the significance of intracellular NO as a more sensitive indicator than conventional anti-oxidative parameters under MPs exposure.

Inactivation of harmful cyanobacteria Microcystis aeruginosa by Cu2+ doped corn stalk biochar treated with different pyrolysis temperatures.

In this study, biochars (BCs) derived from corn stalk treated at various pyrolysis temperatures (350-950 °C) were prepared and then loaded with Cu2+ to form highly efficient algaecide, i.e. Cu2+-doped BC composites (Cu-BCs). The results showed BCs pyrolyzed at higher temperatures suppressed the growth of Microcystis aeruginosa in the order of BC550 ≫ BC750 > BC950, while BC350 accelerated cell growth due to the release of inorganic nutrients. The difference could be attributed to the physicochemical characteristics, including specific surface area, adsorption capacity of nutrients and the presence of particularly persistent free radicals. Furthermore, Cu-BCs exhibited the improved inactivation performance, but the 72 h growth inhibition rates and reaction activities of Cu-BCs were still influenced by the Cu2+ loading ratio and pyrolysis temperature. These results, reported for the first time, demonstrated the algae inactivation efficiency of pristine BCs, and Cu-BCs were principally manipulated by the biochar pyrolysis temperature.

Variation of endosymbiont and citrus tristeza virus (CTV) titers in the Huanglongbing insect vector, Diaphorina citri, on CTV-infected plants.

"Candidatus Liberibacter asiaticus" (CLas) is a notorious agent that causes Citrus Huanglongbing (HLB), which is transmitted by Diaphorina citri (D. citri). We recently found that the acquisition and transmission of CLas by D. citri was facilitated by Citrus tristeza virus (CTV), a widely distributed virus in the field. In this study, we further studied whether different CTV strains manipulate the host preference of D. citri, and whether endosymbionts variation is related to CTV strains in D. citri. The results showed that the non-viruliferous D. citri preferred to select the shoots infected with CTV, without strain differences was observed in the selection. However, the viruliferous D. citri prefered to select the mixed strain that is similar to the field's. Furthermore, D. citri effectively acquired the CTV within 2-12 h depending on the strains of the virus. The persistence period of CTV in D. citri was longer than 24 days, without reduction of the CTV titers being observed. These results provide a foundation for understanding the transmission mode of D. citri on CTV. During the process of CTV acquisition and persistence, the titers of main endosymbionts in D. citri showed similar variation trend, but their relative titers were different at different time points. The titers of the "Candidatus Profftella armatura" and CTV tended to be positively correlated, and the titers of Wolbachia and "Candidatus Carsonella ruddii" were mostly negatively related with titers of CT31. These results showed the relationship among D. citri, endosymbionts, and CTV and provided useful information for further research on the interactions between D. citri and CLas, which may benefit the development of approaches for the prevention of CLas transmission and control of citrus HLB.

Warming-induced phenological mismatch between trees and shrubs explains high-elevation forest expansion.

Despite the importance of species interaction in modulating the range shifts of plants, little is known about the responses of coexisting life forms to a warmer climate. Here, we combine long-term monitoring of cambial phenology in sympatric trees and shrubs at two treelines of the Tibetan Plateau, with a meta-analysis of ring-width series from 344 shrubs and 575 trees paired across 11 alpine treelines in the Northern Hemisphere. Under a spring warming of +1°C, xylem resumption advances by 2-4 days in trees, but delays by 3-8 days in shrubs. The divergent phenological response to warming was due to shrubs being 3.2 times more sensitive than trees to chilling accumulation. Warmer winters increased the thermal requirement for cambial reactivation in shrubs, leading to a delayed response to warmer springs. Our meta-analysis confirmed such a mechanism across continental scales. The warming-induced phenological mismatch may give a competitive advantage to trees over shrubs, which would provide a new explanation for increasing alpine treeline shifts under the context of climate change.

Insulin Glargine is More Suitable Than Exenatide in Preventing Muscle Loss in Non-Obese Type 2 Diabetic Patients with NAFLD.

AIM: This study investigated the effects of insulin glargine and exenatide on the muscle mass of patients with newly diagnosed type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a post-hoc analysis of our previously study, a 24-week randomized controlled multicenter clinical trial (ClinicalTrials.gov, NCT02303730). Seventy-six patients were randomly assigned 1:1 to receive insulin glargine or exenatide treatment. The changes in psoas muscle area (PMA) (mm2) were obtained with the cross-sectional Dixonfat magnetic resonance images at the fourth lumber vertebra. RESULTS: There were no significant differences in age, BMI, gender, and PMA in insulin glargine and exenatide groups at baseline. After treatment, PMA tended to increase by 13.13 (-215.52, 280.80) mm2 in the insulin glargine group and decrease by 149.09 (322.90-56.39) mm2 in the exenatide group (both p>0.05). Subgroup analysis showed a 560.64 (77.88, 1043.40) (mm2) increase of PMA in the insulin group relative to the Exenatide group in patients with BMI<28 kg/m2 (p0.031) after adjusting for gender, age, and research center. Interaction analysis showed an interaction between BMI and treatment (p0.009). However, no interaction was observed among subgroups with a BMI≥28 kg/m2 or with different genders and ages. CONCLUSION: Compared to exenatide, insulin glargine can relativity increase PMA in patients with T2DM having BMI<28 kg/m2 and NAFLD.

Synthesis of Cu2+ doped biochar and its inactivation performance of Microcystis aeruginosa: Significance of synergetic effect.

The harmful cyanobacteria bloom is frequently occurring in the aquatic environment and poses a tremendous threat to both aquatic organisms and ecological function. In this study, a series of Cu2+ doped biochar (BC) composites (Cu-BCs) with different loading ratios (0.1 %-5 wt %) (Cu-BC-0.1/0.5/1/2.5/5) was successfully fabricated through a one-step adsorption method for in-situ inactivation of Microcystis aeruginosa and simultaneous removal of microcystin-LR (MC-LR). Compared with the single BC/CuSO4 and other Cu-BCs composites, the Cu-BC-2.5 exhibited the best algae inactivation performance with the lowest 72 h medium effective concentration (EC50) value of 0.34 mg/L and highest chlorophyll α degradation efficiency of 8.31 g/g. Notably, the as-prepared Cu-BC-2.5 maintained good inactivation performance in the near-neutral pH (6.5-8.5), and the presence of humic acid and salts such as Na2CO3 and NaCl. The outstanding inhibitory effect of the Cu-BC-2.5 could be explained by the synergetic effect between biochar and Cu2+, which greatly elevated reactive oxygen species (ROS) intensity and in turn led to severe membrane damage and collapse of the antioxidant system. Additionally, the Cu-BC-2.5 could simultaneously remove the released microcystin-LR (MC-LR) throughout the inactivation process and prevent secondary pollution, thus offering a new insight into the alleviation of harmful cyanobacteria in aquatic environment.

Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells.

This study investigated the protective effect of lobetyolin (LBT), a Q-marker isolated from the roots of Platycodon grandiflorum (Radix Platycodi), against cisplatin-induced cytotoxicity in human embryonic kidney (HEK293) cells. Results showed that LBT at 20 µM significantly prevented cisplatin-induced cytotoxicity by improving the viability of HEK293 cells, decreasing levels of MDA, and decreasing GSH content triggered by cisplatin. It also suppressed reactive oxygen species (ROS) levels. Molecular docking analysis revealed a strong binding affinity between LBT and the NF-κB protein, with a docking fraction of - 6.5 kcal/mol. These results provide compelling evidence suggesting a potential link between the visualization analysis of LBT and its protective mechanism, specifically implicating the NF-κB signaling pathway. LBT also reduced the expression level of tumor necrosis factor-alpha (TNF-α), phosphorylation NF-κB and IκBα in HEK293 cells which were increased by cisplatin exposure, leading to inhibition of inflammation. Furthermore, western blotting showed that LBT antagonized the up-regulation of Bax, cleaved caspase 3, 8, and 9 expression and inhibited the MAPK signaling pathway by down-regulating phosphorylation JNK, ERK, and p38, partially ameliorating cisplatin-induced cytotoxicity in HEK293 cells. Therefore, these results indicate that LBT has potentially protected renal function by inhibiting inflammation and apoptosis.

Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. AIM OF THE STUDY: This study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Model mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. RESULTS: In vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1ß, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. CONCLUSIONS: These data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent.

Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology.

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (Panax ginseng C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.

Citrus tristeza virus Promotes the Acquisition and Transmission of 'Candidatus Liberibacter Asiaticus' by Diaphorina citri.

Diaphorina citri Kuwayama (D. citri) is an insect vector of phloem-limited 'Candidatus Liberibacter asiatus' (CLas), the presumed pathogen of citrus Huanglongbing (HLB). Recently, our lab has preliminarily found it acquired and transmitted Citrus tristeza virus (CTV), which was previously suggested to be vectored by species of aphids. However, the influences of one of the pathogens on the acquisition and transmission efficiency of the other pathogen remain unknown. In this study, CLas and CTV acquisition and transmission by D. citri at different development stages under field and laboratory conditions were determined. CTV could be detected from the nymphs, adults, and honeydew of D. citri but not from the eggs and exuviates of them. CLas in plants might inhibit CTV acquisition by D. citri as lower CTV-positive rates and CTV titers were detected in D. citri collected from HLB-affected trees compared to those from CLas-free trees. D. citri were more likely to obtain CTV than CLas from host plants co-infected with the two pathogens. Intriguingly, CTV in D. citri facilitated the acquisition and transmission of CLas, but CLas carried by D. citri had no significant effect on the transmission of CTV by the same vector. Molecular detection and microscopy methods confirmed the enrichment of CTV in the midgut after a 72-h acquisition access period. Collectively, these results raise essential scientific questions for further research on the molecular mechanism of pathogen transmission by D. citri and provide new ideas for the comprehensive prevention and control of HLB and CTV.

Current Epidemic Situation and Control Status of Citrus Huanglongbing in Guangdong China: The Space-Time Pattern Analysis of Specific Orchards.

Huanglongbing (HLB) is the most harmful bacterial disease in citrus production in the world, and has been seriously ravaging the citrus groves of South China since the 1930s. The surveillance of the epidemiological characteristics of HLB is of utmost priority for citrus production in this region. In order to explore the effects of disease control measures, analyses on the space-time statistical features of the HLB epidemic, from 2019 to 2021, within six orchards in the Guangdong province are presented. Overall, the number of citrus plants in the orchards usually slightly decreased year by year. The reduction was mainly related to the level of plant susceptibility, which is correlated with citrus varieties. The maximum disease severity (incidence and race increment) was correlated with the awareness of this disease and the management intensity applied by the manager. A higher disease index was found in the conventional management orchards than in the comprehensive prevention and control orchards. Proper insect-protective screen houses can effectively prevent the epidemic of HLB, without affecting the fruit quality, and can also aid with higher yields. A high correlation was found between the geometry and topography of orchards and the HLB epidemic due to the wind direction from May to September and the Asia citrus psyllid activity characteristics. For flat orchards, the incidence of HLB in the north and entrance areas was higher than that in the southwest. In the mountain area, the incidence of the windward side in the south was higher than that of the leeward side in the north. Diseased trees tended to have an edge effect in the grove, whereas the trees of the same disease scale were found clustered in their distribution. These results allow a better understanding of HLB epidemiology and provide guidance for the early warning of HLB in new groves in areas that are severely affected by this disease. Furthermore, they also provide a scientific basis for the comprehensive prevention and control of HLB in old groves.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY: This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS: First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. RESULTS: In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. CONCLUSION: AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

Immunogenic Cell Death in Hematological Malignancy Therapy.

Although the curative effect of hematological malignancies has been improved in recent years, relapse or drug resistance of hematological malignancies will eventually recur. Furthermore, the microenvironment disorder is an important mechanism in the pathogenesis of hematological malignancies. Immunogenic cell death (ICD) is a unique mechanism of regulated cell death (RCD) that triggers an intact antigen-specific adaptive immune response by firing a set of danger signals or damage-associated molecular patterns (DAMPs), which is an immunotherapeutic modality with the potential for the treatment of hematological malignancies. This review summarizes the existing knowledge about the induction of ICD in hematological malignancies and the current research on combining ICD inducers with other treatment strategies for hematological malignancies.