Priming effects of nZVI on carbon sequestration and iron uptake are positively mediated by AM fungus in semiarid agricultural soils.

We investigated the priming effect of nanoscale zero-valent iron (nZVI) on carbon sink and iron uptake, and the possible mediation by AMF (arbuscular mycorrhizal fungi, Funneliformis mosseae) in semiarid agricultural soils. Maize seed dressings comprised of three nZVI concentrations of 0, 1, 2 g·kg-1 and was tested with and without AMF inoculation under high and low soil moistures, respectively. The ICP-OES observations indicated that both low dose of nZVI (1 g·kg-1) and high dose of nZVI (2 g·kg-1) significantly increased the iron concentrations in roots (L: 54.5-109.8 %; H: 119.1-245.4 %) and shoots (L: 40.8-78.9 %; H: 81.1-99.4 %). Importantly, the absorption and translocation rate of iron were substantially improved by AMF inoculation under the low-dose nZVI. Yet, the excess nanoparticles as a stress were efficiently relieved by rhizosphere hyphae, and the iron concentration in leaves and stems can maintain as high as about 300 mg·kg-1 while the iron translocation efficiency was reduced. Moreover, next-generation sequencing confirmed that appropriate amount of nZVI clearly improved the rhizosphere colonization of Funneliformis mosseae (p < 0.001) and the development of soil fungal community. Soil observations further showed that the hyphae development and GRSP (glomalin-related soil protein) secretion were significantly promoted (p < 0.05), with the increased R0.25 (< 0.25 mm) by 35.97-41.16 %. As a return, AMF and host plant turned to input more organic matter into soils for microbial growth and Fe uptake, and such interactions became more pronounced under drought stress. In contrast, high dose of nZVI (2 g·kg-1) tended to agglomerate on the surface of hyphae and spores, causing severe deformation and inactivation of AMF symbionts. Therefore, the priming effects of nZVI on carbon sequestration and Fe uptake in agricultural soils were positively mediated by AMF via the feedback loop of the plant-soil-microbe system for enhanced adaptation to global climate change.

Comparative physiological and soil microbial community structural analysis revealed that selenium alleviates cadmium stress in Perilla frutescens.

Cadmium (Cd) toxicity not only affects plant growth and development, but also affects human health through the food chain. Several studies have demonstrated that Selenium (Se) alleviates Cd stress in plants; however, whether and how Se-alleviated Cd stress by regulating the structure of soil microbial community remain largely unclear. Here, we investigated the alleviating effects of exogenous applied Se (foliar spraying or root application) on plant growth under Cd stress in perilla (Perilla frutescens L.) by measuring the biomass, photosynthetic fluorescence parameters, root cell wall components and soil microbial community structure and diversity. Under Cd stress, perilla seedlings supplemented with Se increased chlorophyll content. Foliar spraying Se increased the levels of relative chlorophyll content (ΦII), photosynthetic system II (ΦPSII) and electron transport rate (ETR) in perilla leaves under Cd stress; while, root application of Se increased the levels of photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), water use efficiency (WUE) and stomatal limitation value (Ls) under Cd stress. Compared with Cd toxicity alone, root application of Se increased the contents of hemicellulosic 1 and hemicellulosic 2 in the cell wall of perilla roots. Cd toxicity or root application of Se did not affect soil bacterial community diversity. Root application of Se increased the relative abundance of Proteobacteria, Bacteroidetes, Fibrobacteres, Sphingomonas and Nitrosospira in Cd-contaminated soil, and thereby improving soil microbial community structure, finally promoting the growth of perilla seedlings.

Efficacy of compound aluminum sulfate injection as a monotherapeutic regimen in non-muscle invasive bladder cancer patients: a retrospective single-arm cohort study.

Background: Compound aluminum sulfate injection (CASI) originated from a Chinese traditional medicine, "Kuzhiye", and has been used in treating non-muscle invasive bladder cancer (NMIBC). Previous studies suggested that CASI was a potential monotherapeutic drug for NMIBC. However, the efficacy and safety of CASI in the treatment of NMIBC, as well as the long-term recurrence after treatment, need to be further evaluated. Methods: A multicenter retrospective single-arm cohort study was conducted. From 2006 to 2009, 101 patients (74 men and 27 women, aged 58.9±11.9 years) with T1 or benign NMIBC were enrolled. Each patient was directly injected with CASI through catheter needle into the root of NMIBC. Vital signs, electrocardiography, blood count, blood biochemistry, and urine analysis were re-examined on day 2 and day 14 after CASI injection, together with a cystoscopic examination 4 weeks after CASI treatment was performed for all patients to assess the clinical activity and safety of CASI. To study long-term efficacy, patients in center 2 were followed up for recurrence with a median follow-up time of 13.8 years. Results: For the 101 patients enrolled in this study, demographic characteristics in the 3 centers showed no significant differences. After CASI, 2 patients showed administration site-dependent, but not dose-dependent, increase in their aluminum concentration in 24 hours without obvious abnormality in blood biochemistry. The overall effective rate was 97.03%, including complete tumor necrosis in 94 patients. Treatment-related adverse events occurred in 20 patients (19.80%), including 9 drug-related and 11 cystoscopy-related adverse events (AEs). All AEs were endurable and disappeared within 2 weeks without any treatment. The maximum tolerated single dose of CASI was 21 mL. Among the 43 patients at center 2, 3 patients were excluded because they changed to other treatment regimen. As of April 2022, of the 40 patients enrolled, 22 had no recurrence and 7 relapsed. The follow-up time was 2-16.2 years. The other 11 patients were lost to follow up. Conclusions: CASI may be an effective and safe option for the treatment of NMIBC and is expected to be a potential monotherapy regimen for NMIBC.

A multicenter, double-blind, placebo-controlled parallel study to evaluate the role of Yinhua Miyanling tablets in the prevention of bacterial biofilm formation on ureteral stents: a randomised trial.

BACKGROUND: Yinhua Miyanling tablet (YMT) not only has the functions of clearing away heat and toxin, dredging drenching and diuresis, but also has antibacterial activity. The formation of bacterial biofilm in ureteral stent and its related infection have plagued the clinic. Antibacterial traditional Chinese medicine is a potential method. METHODS: This multicenter, randomized, double-blind, placebo-controlled study was designed to enroll patients who underwent ureteroscopic lithotripsy associated with indwelling ureteral stents at six centers between March 2019 and June 2020. The eligible patients were randomly assigned to the experimental group to take YMT 2 g qid orally or the control group to take dummy YMT 2 g qid orally from the first day after the operation according to a random number table. The unused drugs were recalled 14±3 days after the operation and record the body temperature. Relevant laboratory tests (urinalysis and urine culture) were performed before extubation. The ureteral stent was removed. The specimen was collected for scanning electron microscopy (SEM). Biofilm formation, USSQ scores, postoperative infectious complications, stone formation, and adverse drug reactions were compared between the two groups. RESULTS: Of the 211 patients enrolled, 165 were included in the per-protocol set (PPS), including 86 in the control group and 79 in the experimental group. No significant difference was found between the two groups in baseline parameters (P>0.05). The prevalence of biofilm formation in the control group (47%) was significantly higher than that in the experimental group (22.7%, P=0.001). There was no significant difference in total USSQ score and domain score between the two groups (all P>0.05). There were more patients with symptomatic urinary tract infection (UTI) in the control group (12.9%) than in the experimental group (2.6%, P=0.017). The incidence of other complications did not show a significant difference between the two groups (all P>0.05). The incidence of stone formation on the ureteral stent surface and adverse drug reactions did not show a significant difference between the two groups (all P>0.05). CONCLUSIONS: YMT is helpful to reduce the formation of bacterial biofilms on ureteral stents and the incidence of symptomatic UTIs related to ureteral stenting after surgery for ureteral calculi. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000041399.

Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance.

Glioblastoma (GBM) is the most lethal primary brain tumor and is highly resistant to current treatments. GBM harbors glioma stem cells (GSCs) that not only initiate and maintain malignant growth but also promote therapeutic resistance including radioresistance. Thus, targeting GSCs is critical for overcoming the resistance to improve GBM treatment. Because the bone marrow and X-linked (BMX) nonreceptor tyrosine kinase is preferentially up-regulated in GSCs relative to nonstem tumor cells and the BMX-mediated activation of the signal transducer and activator of transcription 3 (STAT3) is required for maintaining GSC self-renewal and tumorigenic potential, pharmacological inhibition of BMX may suppress GBM growth and reduce therapeutic resistance. We demonstrate that BMX inhibition by ibrutinib potently disrupts GSCs, suppresses GBM malignant growth, and effectively combines with radiotherapy. Ibrutinib markedly disrupts the BMX-mediated STAT3 activation in GSCs but shows minimal effect on neural progenitor cells (NPCs) lacking BMX expression. Mechanistically, BMX bypasses the suppressor of cytokine signaling 3 (SOCS3)-mediated inhibition of Janus kinase 2 (JAK2), whereas NPCs dampen the JAK2-mediated STAT3 activation via the negative regulation by SOCS3, providing a molecular basis for targeting BMX by ibrutinib to specifically eliminate GSCs while preserving NPCs. Our preclinical data suggest that repurposing ibrutinib for targeting GSCs could effectively control GBM tumor growth both as monotherapy and as adjuvant with conventional therapies.

[Encircling needling combined with physical factor therapy for severe pressure sore].

OBJECTIVE: To compare the clinical efficacy difference between encircling needling combined with physical factor therapy and simple physical factor therapy for severe pressure sore, and to explore the optimal method for severe pressure sores. METHODS: Thirty-four patients with IV-grade pressure sore were randomly divided into an observation group and a control group, 17 cases in each one. Patients in the control group were treated with conventional nursing, ultrasonic wave and short-wave ultraviolet therapy; additionally, the encircling needling was applied in the observation group. All the treatment was given once a day, 5 times a week, and 4-week treatment constituted one session. Totally, two sessions of treatment were performed. Three indices, including the area of pressure sore, 24-h volume of exudates and wound-bed tissue type, were compared between the two groups before and after treatment; the clinical efficacy was evaluated in the two groups. RESULTS: After treatment of one session and two sessions, the area of pressure sore, 24-h volume of exudates and wound-bed tissue type were significantly reduced in the two groups (P < 0.01, P < 0.05), which was more obvious in the observation group (all P < 0.05). The total effective rate in the observation group was 76.5% (13/17) after 1 session and 94.1% (16/17) after 2 sessions, which were superior to 35.3% (6/17) after 1 session and 64.7% (11/17) after 2 sessions in the control group (both P < 0.05). CONCLUSION: Encircling needling combined with physical factor therapy can obviously reduce the pressure sore area and 24-h volume of exudates and improve wound-bed tissue type, which is superior to simple physical factor therapy.

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells.

The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns (DAMPs) can activate immune cells, including dendritic cells (DCs), via Toll-like receptors (TLRs); however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer (CRC) cells treated with oxaliplatin (OXA) and/or 5-fluorouracil (5-Fu) released high levels of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70). After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-1ß, TNF-α, MIP-1α, MIP-1ß, RANTES and IP-10 production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-γ-producing Th1 response both in vitro and in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-γ-producing Th1 response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.

[Clinical evaluation of influence of aspirin on post-operative bleeding after tooth extraction in the elderly].

OBJECTIVE: To investigate the feasibility of continuation of aspirin before tooth extraction in the elderly. METHODS: The patients enrolled in this study were the elderly requiring a single non-impacted tooth extraction. 300 elderly outpatients used lidocaine local infiltration anesthesia, 200 patients without using aspirin before tooth extraction served as control group I, 100 patients with prolong use of aspirin before tooth extraction as observation group I. 300 elderly outpatients used compound articaine local infiltration anesthesia, 200 patients without using aspirin before tooth extraction served as control group II, 100 patients with prolong use of aspirin before tooth extraction as observation group II.Bleedings at 5, 10, 30 min, 24 h after tooth extraction were observed and the relationship between postoperative bleeding and intake of aspirin was analyzed. RESULTS: There was no significant difference at 5, 10, 30 min, 24 h in postoperative bleeding after extraction between control group I and observation group. The incidence of bleeding of observation group II after tooth extraction at 5 min was higher than that of control group II and there was no significant difference at 10, 30 min, 24 h between the two groups. CONCLUSIONS: Continuation of aspirin have no influence on postoperative bleeding. Therefore we suggest that there was no indication to discontinue aspirin for the elderly before a single non-impacted tooth extraction.

An experimental study on the effects of curcumin on posterior capsule opacification in young rabbit eyes.

BACKGROUND: Posterior capsule opacification (PCO) compromises vision development in infants after cataract surgery and lead to amblyopia. To observe the effects of curcumin on PCO in infant rabbits, curcumin was injected under the capaule and into the anterior chamber during phacoemulsification. METHODS: Seventy-five 1-month-old healthy New Zealand white rabbits were randomized into 3 groups, one eye of each rabbit was randomly selected to be operated. The operation involved continuous circular capsulorhexis, followed by hydrodissection with 0.6 ml each of balanced salt solution (BSS, group A), hydroxypropyl-ß-dodextrin (HP-ß-CD, 90 µg/ml, group B) or CUR-HP-ß-CD (123 µg/ml, group C), respectively. After phacoemulsification, 0.4 ml of each drug solution was injected into the anterior chamber via an incision. The extent of corneal edema and the inflammatory response within the anterior chamber were considered as measures PCO and observed postoperatively. All eyes were examined 1 and 2 months postoperative by slit lamp microscopy and photography after pupil dilation. On the third day postoperative, 6 rabbits from each group were executed. Paraffin-embedded sections were stained with hematoxylin-eosin (HE) or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL, indicative of apoptosis). Stained sections were observed under light microscopy. Proliferation of lens epithelial cells (LECs) was observed microscopically on day 3, day 7, month 1 and month 2 after the operation with HE staining. RESULTS: The remission of cornea edema occurred earlier in group C than in groups A and B (P < 0.05); there were no significant differences between groups A and B. The remission of anterior chamber exudation in group C was earlier than those in groups A and B (P < 0.05). No significant difference in the times when PCO occurred, was observed among groups. Compared to groups A and B, the extent of PCO was less severe (P < 0.05). Three days after the operation, LECs aggregated at the orbit. Meanwhile, minor apoptosis was observed in all groups. One month after the operation transparent, cortex and proliferating LECs were observed near the orbit in groups A and B. Two months postoperative, heavy cortex proliferation was observed in all groups: epithelial cells migrated and aggregated at the posterior capsule and rearranged under the anterior capsule in the control group. Proliferation was also observed in group C, but to a less severe extent than in the other two groups. CONCLUSION: CUR-HP-ß-CD exerts an inhibitory effect on PCO.

Effects of wuwei dilong decoction on inflammatory cells and cytokines in asthma model guinea pigs.

OBJECTIVE: To explore the effects and the mechanism of Wuwei Dilong Decoction (Schisandra Fruit and Earthworm Decoction) for treatment of asthma. METHODS: The asthma guinea pig model was established with spray of ovalbumin (OVA). Fifteen days later, the guinea pigs were administered by intra-gastric perfusion of Wuwei Dilong Decoction once a day for 8 consecutive days. Blood samples were taken for testing the total leucocytes, eosinophil (EOS), lymphocytes, interferon-gamma (IFN-gamma) and leukotriene B4 (LTB4). RESULTS: In the asthma model group, the total leucocytes, EOS and lymphocytes were all increased, with significant differences as compared with the different dosage Wuwei Dilong Decoction groups (P < 0.01 or P < 0.05). The serum LTB4 in the asthma model group was significantly increased and IFN-gamma decreased. After administration of Wuwei Dilong Decoction of the large, medium and small dosages, LTB4 decreased, while IFN-gamma increased (P < 0.05 or P < 0.01). CONCLUSION: Wuwei Dilong Decoction can inhibit infiltration and diffusion of the inflammatory cells in the asthma model guinea pigs, and regulate LTB4 and IFN-gamma, which is probably one of the important mechanisms of Wuwei Dilong Decoction for relieving asthma.

[Effect of earthworm decoction on airway inflammation of bronchial asthma in guinea pigs].

OBJECTIVE: To investigate the effect of Earthworm decoction on the airway inflammation of experimental bronchial asthma in guinea pigs and inquire into the mechanism in the decoction. METHOD: Forty-eight guinea pigs were randomly divided into six groups: the control group, the model group, the dexamethasone group, the Xiaoqinglong decoction group, the earthworm decoction large dosage group and the Earthworm decoction low dosage group, 8 guinea pigs in each group. Except the control group, the other groups were sensitized with ovalbumin (OVA) by a combination of intraperitional injection and repeated intranasal challenges to establish the guinea pigs asthma model. However, in the control group, normal saline was used. The morphological changes of bronchial tube, the lung tectology and the inflammation germ cell quantity of eosinophils (Eos), lymphocytes (Ly), neutrophils (Neu) and total blood cells in the blood and bronchoalveolar lavaga fluid (BALF) were examinated in each group respectively. RESULT: The levels of Eos, Ly, Neu and total cell quantity in the blood and BALF after the earthworm decoction treatment in the large dosage group were significantly lower than those in the model group (P <0.01), and in the low dosage group were lower too (P <0.05). The Earthworm decoction large dosage could obviously improve the bronchial tube epidermis damage, the mucous membrane gland proliferation and hydrops, asthma pathology change and basilar membrane accumulation. Eos apoptosis was obsered in the bronchoalveolar, blood and BALF. The Earthworm decoction small dosage had a similar effect but slightly to the large dosage. CONCLUSION: The Earthworm decoction can lighten the airway inflammation in asthmatic guinea pigs, its mechanism is related with the inhibition of Eos infiltration, acceleration of Eos apoptosis and improvement of the bronchial tube and the lung tectology changes. The effect of the decoction is dose-dependent.