Functionality of arbuscular mycorrhizal fungi varies across different growth stages of maize under drought conditions.

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation.

Efficacy of remimazolam tosilate versus propofol for total intravenous anaesthesia in urological surgery: A randomised clinical trial.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that acts on the gamma-aminobutyric acid type A receptor (GABAAR). OBJECTIVE: To compare the efficacies of remimazolam (RMZ), and propofol (PROP) combined with remifentanil and cisatracurium for total intravenous anaesthesia (TIVA) in patients undergoing urological surgery. DESIGN: A prospective, single-blind, randomised, noninferiority clinical trial. SETTING: Single centre from 1 January 2022 to 30 March 2022. PATIENTS: A total of 146 adult patients undergoing elective urological surgery. INTERVENTION: Patients were randomly allocated in a 1 : 1 ratio to the PROP or RMZ groups. In the PROP group, anaesthesia was induced with propofol at 100 mg min -1 to reach a bispectral index score (BIS) of 40 to 60. After loss of consciousness (LOC), intravenous fentanyl 3 µg kg -1 was administered, followed by cisatracurium 0.3 mg kg -1 . Patients were intubated 3 min after cisatracurium administration. Anaesthesia was maintained with the combination of propofol (plasma concentration: 2.5 to 4 µg ml -1 ) and remifentanil (plasma concentration: 2.5 to 4 ng ml -1 ). In the RMZ group, anaesthesia was induced with remimazolam tosilate starting at 10 mg kg -1  h -1 to reach a BIS of 40 to 60 and maintained between 0.2 and 2 mg kg -1  h -1 . After LOC, fentanyl and cisatracurium were administered and intubation was performed as in the PROP group. Anaesthesia was maintained with a combination of remimazolam (0.2 to 2 mg kg -1  h -1 ) and remifentanil (plasma concentration: 2.5 to 4 ng ml -1 ). MAIN OUTCOME MEASURES: The primary outcome was the TIVA success rate. The predefined noninferiority margin considered an absolute difference of 6% in the primary outcome between the groups. The secondary outcomes were vital signs, anaesthesia and surgery characteristics, and adverse events. RESULTS: All patients completed the trial. The success rates of TIVA with remimazolam and propofol were 100 and 98.6%, respectively. The incidence of hypotension during anaesthesia was lower in the RMZ group (26%) than in the PROP group (46.6%) ( P  = 0.016). The median [IQR] total consumption of ephedrine during anaesthesia was higher in the PROP group 10 [0 to 12.5] mg than in the RMZ group 0 [0 to 10] mg ( P  = 0.0002). The incidence of injection pain was significantly higher in the PROP group (76.7%) than in the RMZ group (0; P  < 0.001). No significant differences in the controllability of the anaesthesia depth, anaesthesia and surgery characteristics, or vital signs were observed between the groups. CONCLUSION: Remimazolam demonstrated noninferior efficacy to propofol combined with remifentanil and cisatracurium for TIVA in patients undergoing urological surgery. TRIAL REGISTRATION: Chictr.org.cn, identifier: ChiCTR2100050923. CLINICAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100050923, Principal investigator: Xuehai Guan, Date of registration: 8 November 2021, https://www.chictr.org.cn/showproj.html?proj=133466 ).

Recovery and utilization of waste filtrate from industrial biological fermentation: Development and metabolite profile of the Bacillus cereus liquid bio-fertilizer.

Most fermentation waste filtrates can be used as raw materials for producing bio-fertilizers to reduce wastewater emissions and environmental pollution, but their bio-fertilizer utilization depends on the nutrients contained and their metabolized by functional microorganism. To achieve bio-fertilizer utilization of Acremonium terricola fermented waste filtrate, this study systematically explored the functional microbial species for making good use of waste liquid, optimized material process parameters for bio-fertilizer production based on D-optimal mixture design method, and analyzed the composition of the waste filtrate and its metabolism by functional microorganisms using a non-targeted LC-MS metagenomics technique. The results showed that Bacillus cereus was the functional microbial candidate for producing bio-fertilizer because of its more efficiently utilize the waste filtrate than other Bacillus sp. The optimal material process parameters of the liquid bio-fertilizer were the inoculum dose of 5% (v:v, %), 80% of waste filtrate, 0.25% of N, 3.5% of P2O5, 3.25% of K2O of mass percentage. Under these conditions, the colony forming unit (CFU) of Bacillus cereus could reach (1.59 ± 0.01) × 108 CFU/mL, which met the bio-fertilizer standard requirements of the People's Republic of China (NY/T798). Furthermore, the potential functions of bio-fertilizer were studied based on comparison of raw materials and production components: on the one hand, waste filtrate contained abundant of nitrogen and carbon sources, and bioactive substances secreted by Acremonium terricola, such as ß-alanyl-L-lysine, anserine, UMP, L-lactic acid and etc., which could meet the nutrient requirements of the growth of Bacillus cereus; On the other hand, some compounds of waste filtrate with the potential to benefit the plant growth and defense, such as betaine aldehyde, (2E,6E)-farnesol, homogentisic acid and etc., were significantly up regulated by Bacillus cereus utilization of the filtrate. To sum up, this work highlighted that the waste filtrate could be efficiently developed into liquid bio-fertilizer by Bacillus cereus.

Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor.

BACKGROUND: The morbidity and mortality of sepsis are extremely high, which is a major problem plaguing human health. However, current drugs and measures for the prevention and treatment of sepsis have little effect. Sepsis-associated acute liver injury (SALI) is an independent risk factor for sepsis, which seriously affects the prognosis of sepsis. Studies have found that gut microbiota is closely related to SALI, and indole-3-propionic Acid (IPA) can activate Pregnane X receptor (PXR). However, the role of IPA and PXR in SALI has not been reported. METHODS: This study aimed to explore the association between IPA and SALI. The clinical data of SALI patients were collected and IPA level in feces was detected. The sepsis model was established in wild-type mice and PXR knockout mice to investigate the role of IPA and PXR signaling in SALI. RESULTS: We showed that the level of IPA in patients' feces is closely related to SALI, and the level of IPA in feces has a good ability to identify and diagnose SALI. IPA pretreatment significantly attenuated septic injury and SALI in wild-type mice, but not found in knockout PXR gene mice. CONCLUSIONS: IPA alleviates SALI by activating PXR, which reveals a new mechanism of SALI, and provides potentially effective drugs and targets for the prevention of SALI.

The difference in mean arterial pressure induced by remimazolam compared to etomidate in the presence of fentanyl at tracheal intubation: A randomized controlled trial.

Background: Combined use of hypnotic and opioids during anesthesia inductions decreases blood pressure. Post-induction hypotension (PIHO) is the most common side effect of anesthesia induction. We aimed to compare the difference in mean arterial pressure (MAP) induced by remimazolam with that induced by etomidate in the presence of fentanyl at tracheal intubation. Methods: We assessed 138 adult patients with American Society of Anesthesiologists physical status I-II who underwent elective urological surgery. Patients were randomly allocated to receive either remimazolam or etomidate as alterative hypnotic in the presence of fentanyl during anesthesia induction. Comparable BIS values were achieved in both groups. The primary outcome was the difference in the MAP at tracheal intubation. The secondary outcomes included the characteristics of anesthesia, surgery, and adverse effects. Results: The MAP was higher in the etomidate group than in the remimazolam group at tracheal intubation (108 [22] mmHg vs. 83 [16] mmHg; mean difference, -26; 95% confidence interval [CI], -33 to -19; p < 0.0001). Heart rate was significantly higher in the etomidate group than in the remimazolam group at tracheal intubation. The patients' condition warranted the administration of ephedrine more frequently in the remimazolam group (22%) than in the etomidate group (5%) (p = 0.0042) during anesthesia induction. The remimazolam group had a lower incidence of hypertension (0% vs. 9%, p = 0.0133), myoclonus (0% vs. 47%, p < 0.001), and tachycardia (16% vs. 35%, p = 0.0148), and a higher incidence of PIHO (42% vs. 5%, p = 0.001) than the etomidate group during anesthesia induction. Conclusion: Remimazolam was associated with lower MAP and lower heart rate compared to etomidate in the presence of fentanyl at tracheal intubation. Patients in the remimazolam group had a higher incidence of PIHO, and their condition warranted the administration of ephedrine more frequently than in the etomidate group during anesthesia induction.

Cyclin D1 mediates pain behaviour in a rat model of breast cancer-induced bone pain by a mechanism involving regulation of the proliferation of spinal microglia.

AIMS: The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. METHODS: Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. RESULTS: IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. CONCLUSION: Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP.Cite this article: Bone Joint Res 2022;11(11):803-813.

Crosstalk between gut microbiota and renal ischemia/reperfusion injury.

Renal ischemia-reperfusion injury (IRI) is the main cause of acute kidney injury and the cause of rapid renal dysfunction and high mortality. In recent years, with the gradual deepening of the understanding of the intestinal flora, exploring renal IRI from the perspective of the intestinal flora has become a research hotspot. It is well known that the intestinal flora plays an important role in maintaining human health, and dysbiosis is the change in the composition and function of the intestinal tract, which in turn causes intestinal barrier dysfunction. Studies have shown that there are significant differences in the composition of intestinal flora before and after renal IRI, and this difference is closely related to the occurrence and development of renal IRI and affects prognosis. In addition, toxins produced by dysregulated gut microbes enter the bloodstream, which in turn exacerbates kidney damage. This article reviews the research progress of intestinal flora and renal IRI, in order to provide new treatment ideas and strategies for renal IRI.

Efficacy of Pre-Treatment with Remimazolam on Prevention of Propofol-Induced Injection Pain in Patients Undergoing Abortion or Curettage: A Prospective, Double-Blinded, Randomized and Placebo-Controlled Clinical Trial.

BACKGROUND: Propofol-induced injection pain (PIP) is a well-known problem in general anesthesia. We hypothesized that pre-treatment with remimazolam prevents PIP in patients undergoing abortion or curettage. MATERIALS AND METHODS: In this prospective, single-center, double-blinded, randomized, placebo-controlled clinical trial, adult patients aged 18 to 60 undergoing abortion or curettage were randomly assigned to three groups. Group Lido received system lidocaine (a bolus of 0.5 mg kg-1, iv). Group Remi received remimazolam (a bolus of 0.1 mg kg-1, iv). Group NS received identical volumes of 0.9% normal saline. Sixty seconds after the injection of lidocaine, remimazolam or saline, patients were injected with propofol at a rate of 12 mL/min until the loss of consciousness. The primary outcome was the incidence of PIP at the time of induction using 4-point scale. Secondary outcomes included propofol-induced injection pain, vital signs, the characteristics of anesthesia and surgery, and adverse events. RESULTS: The incidence of patients with PIP was higher in group NS than that in group Lido and group Remi (75.7, 44.3, and 42.9%, respectively, p < 0.001). The percentages of patients with moderate PIP were higher in group NS than that in group Lido and group Remi (20.0, 2.9, and 1.4%, respectively, p < 0.001). Moreover, the consumption of propofol and the incidence of adverse event (hypoxemia and chin lifting) in group Remi were lower than that in group NS and Lido, and less patients got physical movement and cough in group Remi. The recovery time in group NS was longer than that in group Lido and Remi. CONCLUSION: Our findings indicate that pre-treatment with remimazolam reduced the incidence and intensity of PIP in abortion or curettage patients, equivalent to that of lidocaine without severe adverse effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR2100041805).

Mifepristone polymorph with enhanced solubility, dissolution and oral bioavailability.

Mifepristone is one of potent anti-progesterone agents, which binds to progesterone receptors and glucocorticoid receptors. Until now, there are a lot of research focusing on enhancing the solubility and oral bioavailability of Mifepristone. However, poor solubility and oral bioavailability has some undesirable consequences. In this work, Mifepristone in form D was discovered for the first time and characterized by PXRD, TGA, DSC, FT-IR, SEM and SS NMR. Form D was a metastable crystal type which manifested favorable stability under ambient conditions. Form D had better dissolution characteristic compared with commercial Mifepristone in 0.5% SDS solution. In addition, Mifepristone in form D exhibited a 1.43-fold higher peak plasma concentration (Cmax) and 1.46-fold higher area under the curve (AUC) in rats. The work in this paper is a complement to the present understanding of drug polymorphism on the in vitro and in vivo behavior, and establishes the ground work for future development of Mifepristone in form D as a promising drug for the market.

In situ high-potential-driven surface restructuring of ternary AgPd-Ptdilute aerogels with record-high performance improvement for formate oxidation electrocatalysis.

Engineering nanoparticle surfaces driven by various gas atmospheres has attracted intensive attention in the design of efficient electrocatalysts for sustainable energy applications. However, the development of a more facile and efficient in situ engineering strategy under electrochemical testing conditions to achieve surface-reconstruction-induced high performance is significantly lacking. Herein, for the first time, we report in situ high-potential-driven restructuring in ternary AgPdPt aerogels with dilute Pt (AgPd-Ptdilute) during the electrochemical cyclic voltammetry testing for the alkaline formate oxidation reaction (FOR), in which the upper potential limit is ingeniously extended to the Ag redox region. Impressively, the resulting AgPd-Ptdilute aerogel displayed remarkable structural and compositional reconstruction in an alkaline environment. Our comprehensive results revealed that the high-potential cycling induces unique Ag outward diffusion to form an enriched PdPt metallic surface atomically coupled with amorphous Ag2O, which provides more opportunities to expose abundant active sites and induce robust electronic structure modulation. Notably, the surface-restructured AgPd-Ptdilute aerogel achieved record-high activity for FOR when the upper potential limit was extended to 1.3 V, exhibiting an unprecedented 5-fold improvement in activity compared to that of the commercial Pd/C. Moreover, it also offered greatly enhanced electrochemical stability with negligible activity decay after 500 cycles. This work gives a good understanding of surface reconstruction during such a novel high-potential-driven cycling process and opens a new door to designing more efficient electrocatalysts for FOR and beyond.

Sorghumol triterpene inhibits the growth of circulating renal cancer cells by promoting cell apoptosis, G2/M cell cycle arrest and downregulating m-TOR/PI3K/AKT signalling pathway.

PURPOSE: To investigate the growth inhibitory effect of Sorghumol on the circulating renal cancers cells and to investigate the underlying mechanisms including its effects on apoptosis, cell cycle phase distribution and m-TOR/PI3K/AKT signalling pathway. METHODS: The antiproliferative effects were assessed by WST-1 and colony formation assay. Apoptosis was detected by the Hoechst and AO/EB staining using fluorescence microscopy. Cell cycle analysis was carried out by flow cytometry. Protein expression was checked by western blotting. RESULTS: The results revealed that Sorghumol inhibited the growth of the renal cancer cell (RCC) line A498 and circulating RCCs. However, more profound effects were observed on the RCC cells. The anticancer effects were found to be due to induction of apoptosis. Moreover, Sorghumol could also caused G2/M cell cycle arrest of the RCC cells. Besides, examination of the effect of Sorghumol on m-TOR/PI3K/AKT revealed that Sorghumol inhibited the expression of p-mTOR, p-PI3K and p-AKT in a concentration-dependent manner. CONCLUSION: Taken together, we conclude that Sorghumol inhibited the proliferation of circulating RCCs and may therefore prove to be an important lead molecule for the treatment of renal cancer.