A CTL - Lys immune function maintains insect metamorphosis by preventing gut bacterial dysbiosis and limiting opportunistic infections.

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Predicting Portal Pressure Gradient in Patients with Decompensated Cirrhosis: A Non-invasive Deep Learning Model.

BACKGROUND: A high portal pressure gradient (PPG) is associated with an increased risk of failure to control esophagogastric variceal hemorrhage and refractory ascites in patients with decompensated cirrhosis. However, direct measurement of PPG is invasive, limiting its routine use in clinical practice. Consequently, there is an urgent need for non-invasive techniques to assess PPG. AIM: To develop and validate a deep learning model that predicts PPG values for patients with decompensated cirrhosis and identifies those with high-risk portal hypertension (HRPH), who may benefit from early transjugular intrahepatic portosystemic shunt (TIPS) intervention. METHODS: Data of 520 decompensated cirrhosis patients who underwent TIPS between June 2014 and December 2022 were retrospectively analyzed. Laboratory and imaging parameters were used to develop an artificial neural network model for predicting PPG, with feature selection via recursive feature elimination for comparison experiments. The best performing model was tested by external validation. RESULTS: After excluding 92 patients, 428 were included in the final analysis. A series of comparison experiments demonstrated that a three-parameter (3P) model, which includes the international normalized ratio, portal vein diameter, and white blood cell count, achieved the highest accuracy of 87.5%. In two distinct external datasets, the model attained accuracy rates of 85.40% and 90.80%, respectively. It also showed notable ability to distinguish HRPH with an AUROC of 0.842 in external validation. CONCLUSION: The developed 3P model could predict PPG values for decompensated cirrhosis patients and could effectively distinguish HRPH.

Palladium-Catalyzed Esterification of Aryl Fluorosulfates with Aryl Formates.

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

Silencing of the calcium-dependent protein kinase TaCDPK27 improves wheat resistance to powdery mildew.

BACKGROUND: Calcium ions (Ca2+), secondary messengers, are crucial for the signal transduction process of the interaction between plants and pathogens. Ca2+ signaling also regulates autophagy. As plant calcium signal-decoding proteins, calcium-dependent protein kinases (CDPKs) have been found to be involved in biotic and abiotic stress responses. However, information on their functions in response to powdery mildew attack in wheat crops is limited. RESULT: In the present study, the expression levels of TaCDPK27, four essential autophagy-related genes (ATGs) (TaATG5, TaATG7, TaATG8, and TaATG10), and two major metacaspase genes, namely, TaMCA1 and TaMCA9, were increased by powdery mildew (Blumeria graminis f. sp. tritici, Bgt) infection in wheat seedling leaves. Silencing TaCDPK27 improves wheat seedling resistance to powdery mildew, with fewer Bgt hyphae occurring on TaCDPK27-silenced wheat seedling leaves than on normal seedlings. In wheat seedling leaves under powdery mildew infection, silencing TaCDPK27 induced excess contents of reactive oxygen species (ROS); decreased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); and led to an increase in programmed cell death (PCD). Silencing TaCDPK27 also inhibited autophagy in wheat seedling leaves, and silencing TaATG7 also enhanced wheat seedling resistance to powdery mildew infection. TaCDPK27-mCherry and GFP-TaATG8h colocalized in wheat protoplasts. Overexpressed TaCDPK27-mCherry fusions required enhanced autophagy activity in wheat protoplast under carbon starvation. CONCLUSION: These results suggested that TaCDPK27 negatively regulates wheat resistance to PW infection, and functionally links with autophagy in wheat.

[Clinical features of autoimmune glial fibrillary acidic protein astrocytopathy in children: an analysis of 34 cases]. / 34ä¾‹å°å„¿è‡ªèº«å ç–«æ€§èƒ¶è´¨çº¤ç»´é ¸æ€§è›‹ç™½æ˜Ÿå½¢èƒ¶è´¨ç»†èƒžç— çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). METHODS: A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis. RESULTS: The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis. CONCLUSIONS: Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.

Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.

The Calcium-Dependent Protein Kinase TaCDPK27 Positively Regulates Salt Tolerance in Wheat.

As essential calcium ion (Ca2+) sensors in plants, calcium-dependent protein kinases (CDPKs) function in regulating the environmental adaptation of plants. However, the response mechanism of CDPKs to salt stress is not well understood. In the current study, the wheat salt-responsive gene TaCDPK27 was identified. The open reading frame (ORF) of TaCDPK27 was 1875 bp, coding 624 amino acids. The predicted molecular weight and isoelectric point were 68.905 kDa and 5.6, respectively. TaCDPK27 has the closest relationship with subgroup III members of the CDPK family of rice. Increased expression of TaCDPK27 in wheat seedling roots and leaves was triggered by 150 mM NaCl treatment. TaCDPK27 was mainly located in the cytoplasm. After NaCl treatment, some of this protein was transferred to the membrane. The inhibitory effect of TaCDPK27 silencing on the growth of wheat seedlings was slight. After exposure to 150 mM NaCl for 6 days, the NaCl stress tolerance of TaCDPK27-silenced wheat seedlings was reduced, with shorter lengths of both roots and leaves compared with those of the control seedlings. Moreover, silencing of TaCDPK27 further promoted the generation of reactive oxygen species (ROS); reduced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); aggravated the injury to photosystem II (PS II); and increased programmed cell death (PCD) in wheat leaves under NaCl treatment, confirming that the TaCDPK27-silenced seedlings exhibited more NaCl injury than control seedlings. Taken together, the decrease in NaCl tolerance in TaCDPK27-silenced seedlings was due to excessive ROS accumulation and subsequent aggravation of the NaCl-induced PCD. TaCDPK27 may be essential for positively regulating salt tolerance in wheat seedlings.

A prospective randomized controlled study on mouse nerve growth factor in the treatment of global developmental delay in children. / é¼ ç¥žç»ç”Ÿé•¿å› å­æ²»ç–—å ¨é¢æ€§å‘è‚²è¿Ÿç¼“çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.

[Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine].

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1ß and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.

[Multi-targeted therapeutic effects of Huangkui Capsules on insulin resistance and urine microalbumin in early diabetic kidney disease patients].

To observe the multi-targeted therapeutic effects of Huangkui Capsules(HKC)on insulin resistance(IR)and urine microalbumin in the early diabetic kidney disease(DKD)patients. The case data from the 83 DKD patients at G2 and A2 stage were collected respectively and analyzed retrospectively. According to the different treatment,all patients were divided into the control(A)group(40 cases)and the treated(B)group(43 cases). Among them,the A group patients were received "routine basic treatment";the B group patients were received "routine basic treatment+HKC". For the 2 group patients,firstly,the baseline parameters before receiving the treatment were compared respectively,and then,the changes of the total scores of traditional Chinese medicine(TCM) syndromes and the indicators of IR,urine protein,renal function,blood lipids and safety after receiving the treatment for 8 weeks were compared,respectively. Furthermore,for the all patients,the correlation analysis between IR and urine protein or IR and the total scores of TCM syndromes was carried out,respectively. The results showed that,for the B group patients received "routine basic treatment",their total scores of TCM syndromes,urine protein indicators including urine microalbumin(micro-UAlb) and urine microalbumin/urinary creatinine(UACR),IR indicators including fasting serum insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly improved,respectively. For the all DKD patients,before and after the treatment,the main IR indicators(FIN and HOMA-IR)were positively correlated with urine protein indicators(micro-UAlb and UACR). The main IR indicators(FIN and HOMA-IR) were also positively correlated with the total scores of TCM syndromes. In addition,2 treatments had no significant effects on renal function,blood lipids and safety indicators in the all DKD patients. Overall, "routine basic treatment+HKC" can ameliorate IR and reduce urine microalbumin in the early DKD patients. Its therapeutic targets may be not only proteinuria,but also IR,which is the upstream risk factor of proteinuria.

[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways].

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 µg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated ß-galactosidase(SA-ß-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Molecular characterization of immune responses of Helicoverpa armigera to infection with the mermithid nematode Ovomermis sinensis.

BACKGROUND: Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. RESULTS: Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. CONCLUSIONS: This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.

Inactivation of TSC1 promotes epithelial-mesenchymal transition of renal tubular epithelial cells in mouse diabetic nephropathy.

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the potential mechanisms of renal fibrosis, which promotes the development of diabetic nephropathy (DN). However, the molecular mechanisms of EMT remain largely unknown. Tuberous sclerosis proteins TSC1 and TSC2 are key integrators of growth factor signaling, and the loss of TSC1 or TSC2 function leads to a spectrum of diseases that underlie abnormalities in cell growth, proliferation, differentiation, and migration. In this study, we investigated the effects of TSC1 on high glucose (HG)-induced EMT of human proximal tubular epithelial HK-2 cells in vitro and renal fibrosis in TSC1-/- and db/db mice. We found that the exposure of HK-2 cells to HG (30 mM) time-dependently decreased TSC1 expression, increased the phosphorylation of mTORC1, P70S6K, and 4E-BP-1, and promoted cell migration, resulting in EMT. Transfection of the cells with TSC1 mimic significantly ameliorated HG-induced EMT of HK-2 cells. The tubules-specific TSC1 knockout mice (TSC1-/-) displayed a significant decline in renal function. TSC1-/- mice, similar to db/db mice, showed greatly activated mTORC1 signaling and EMT process in the renal cortex and exacerbated renal fibrosis. Overexpression of TSC1 through LV-TSC1 transfection significantly alleviated the progression of EMT and renal fibrosis in the renal cortex of db/db mice. Taken together, our results suggest that TSC1 plays a key role in mediating HG-induced EMT, and inhibition of TSC1-regulated mTORC1 signaling may be a potential approach to prevent renal fibrosis in DN.

Phytoextraction of initial cutting of Salix matsudana for Cd and Cu.

Salix species are widely used as vegetation filters because of their flourishing root system and fast growth rate. However, studies have yet to determine whether the root system functions in vegetable filters with mixed heavy metal (HM) pollution or whether initial cutting participates in the phytoextraction of HMs. This study aims to determine the function of the root system and initial cutting as vegetation filters in the absorption and accumulation of Cd and Cu. Thick (>1 cm in diameter) and fine (<1 cm in diameter) initial cuttings of Salix matsudana were planted in a nutrient solution with single and mixed (Cd + Cu) treatments. The roots of several initial cuttings were removed daily to eradicate rhizofiltration. Results revealed that the existence of the root system altered distribution and interaction of Cd and Cu in plant organs and enhanced tolerance and phytoextraction capacity of plants. The initial cuttings could also absorb and accumulate HMs in the early growth stages of willow without roots. Cu inhibited the plant absorption and accumulation of Cd and promoted Cd transport to shoots. Cd inhibited the Cu absorption of the root system. Our study provided essential data regarding woody species as vegetation filters of HM pollution.

[Impacts of electromagnetic radiation from cellphones and Wi-Fi on spermatogenesis].

With the development of Wi-Fi technology and widespread exposure to electromagnetic radiation (EMR), people are increasingly concerned about the health hazards caused by radiofrequency electromagnetic fields as from cellphones and Wi-Fi, particularly about the current decline in sperm concentration and increase in male infertility. Long-term exposure to EMR not only damages male reproductive organs, but also affects the number, morphology, motility and oocyte-binding ability of sperm, and indirectly increases the risk of infertility. However, EMR is not unavoidable. Low-intensity short-term or intermittent exposure to EMR has little adverse effect on reproductive organs and sperm. And many antioxidant and anti-free radical agents, such as vitamin E and melatonin, can protect some special populations from EMR. This review presents an overview of the impacts of EMR from cellphones and Wi-Fi on sperm, some countermeasures, and prospects of EMR protection.

[Influence of online social software on HIV transmission among men who have sex with men].

The prevention and control of human immunodeficiency virus (HIV) infection is important for public health. Sexual contact transmission has replaced blood transmission as a major route of HIV transmission in China. The incidence of HIV infection increased significantly among young men who have sex with men (MSM). Online social software instead of traditional venues has become a main means of seeking sexual partners. The application of online social software may contribute to an increased incidence of HIV among young MSMs by promoting such risky behaviors as having occasional or multiple sexual partners and drug abuse. Compared with the MSMs enrolled from traditional venues, those recruited online showed significant differences in the educational level, sexual behaviors, and HIV knowledge. Online social software is a promising way to improve the prevention and control of HIV as well as HIV-related epidemic surveys.

[Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine].

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

[Triptolide inhibits NLRP3 inflammasome activation and ameliorates podocyte epithelial-mesenchymal transition induced by high glucose].

The aim of this paper was to explore the effects of triptolide( TP),the effective component of Tripterygium wilfordii on improving podocyte epithelial-mesenchymal transition( EMT) induced by high glucose( HG),based on the regulative mechanisms of Nod-like receptor protein 3( NLRP 3) inflammasome in the kidney of diabetic kidney disease( DKD). The immortalized podocytes of mice in vitro were divided into the normal( N) group,the HG( HG) group,the low dose of TP( L-TP) group,the high dose of TP( HTP) group and the mannitol( MNT) group,and treated by the different measures,respectively. More specifically,the podocytes in each group were separately treated by D-glucose( DG,5 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) + TP( 5 µg·L~(-1))or HG( 30 mmol·L~(-1)) + TP( 10 µg·L~(-1)) or DG( 5 mmol·L~(-1)) + MNT( 24. 5 mmol·L~(-1)). After the treatment of HG or TP at 24,48 and 72 h,firstly,the activation of podocyte proliferation was investigated. Secondly,the protein expression levels of the epithelial markers in podocytes such as nephrin and ZO-1,the mesenchymal markers such as collagen Ⅰ and fibronectin( FN) were detected,respectively. Finally,the protein expression levels of NLRP3 and apoptosis-associated speck-like protein( ASC) as the key signaling molecules of NLRP3 inflammasome activation,as well as the downstream effector proteins including caspase-1,interleutin( IL)-1ß and IL-18 were examined,severally. The results indicated that,for the cultured podocytes in vitro,HG could cause the low protein expression levels of nephrin and ZO-1,induce the high protein expression levels of collagen Ⅰ and FN and trigger podocyte EMT. Also HG could cause the high protein expression levels of NLRP3,ASC,caspase-1,IL-1ß and IL-18 and induce NLRP3 inflammasome activation. On the other hand,the co-treatment of TP( L-TP or H-TP) and HG for podocytes could recover the protein expression levels of nephrin and ZO-1,inhibit the protein expression levels of collagen Ⅰ and FN and ameliorate podocyte EMT. Also the co-treatment of TP( L-TP or H-TP) and HG could down-regulate the protein expression levels of NLRP3 and ASC,inhibit NLRP3 inflammasome activation and reduce the protein expression levels of the downstream effector molecules including caspase-1,IL-1ß and IL-18. On the whole,HG could activate NLRP3 inflammasome and induce podocyte EMT in vitro. TP at the appropriate dose range could inhibit NLRP3 inflammasome activation and ameliorate podocyte EMT,which may be one of the critical molecular mechanisms of TP protecting againstpodocyte inflammatory injury in DKD.