Silencing TRPM2 enhanced erastin- and RSL3-induced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins.

Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. Cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival. Our bioinformatic analysis revealed that TRPM2 is associated with cellular responses to chemical stimulus and oxidative stress, implying the potential role of TRPM2 in ferroptosis. Gastric cancer cells were treated with the ferroptosis-inducer, Erastin and RSL3. siRNA transfection was used to silence TRPM2. The levels of GSH, Fe2+, ROS and lipid peroxidation, and the activity of GPx activity were evaluated by flow cytometry and spectrophotometer. The effect of TRPM2 on ubiquitination of HIF-1α and Nrf2 were evaluated by co-immunoprecipitation. Erastin and RSL3 induced the up-regulation of TRPM2 in gastric cancer cell lines, especially in SGC7901 and MGC803. These two cells also showed stronger resistance to Erastin and RSL3 than the other cell lines. TRPM2 knockdown reduced the concentration of GSH and GPx activity, but enhanced the concentration of Fe2+, ROS and lipid peroxidation, which are significant indicators of ferroptosis. Importantly, silencing TRPM2 enhanced the inhibitory effects of Erastin and RSL3 on gastric cancer cell viability, migration, and invasion. TRPM2 stabilized and finally elevated the abundance of HIF-1α and Nrf2 in SGC7901 and MGC803 cells upon Erastin and RSL3. Activation of HIF-1α impaired Erastin- and RSL3-induced ferroptosis after TRPM2 knockdown. Collectively, silencing TRPM2 enhanced Erastin- and RSL3-induced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00545-z.

Efficacy and safety of integrated traditional Chinese and Western medicine against COVID-19: A systematic review and meta-analysis.

Although plenty of clinical trials have confirmed the efficacy and safety of integrated traditional Chinese and Western medicine (ITCWM) against COVID-19, the role of ITCWM remains controversial. So we conducted a systematic review and meta-analysis of published studies in eight major databases that report the outcomes of interest in COVID-19 patients receiving ITCWM. RevMan5.4 software was used for meta-analysis, while the quality of RCTs was assessed by the Cochrane risk of bias tool and the retrospective studies were assessed by Newcastle-Ottawa Scale. Eventually, a total of 53 studies with 5425 COVID-19 patients was identified. The meta-analysis results showed that ITCWM was significantly better than western medicine treatment (WMT) alone in the percentage of cases changing to severe/critical [RR = 0.40, 95%CI (0.33, 0.49), p < .00001, I2  = 10%], overall clinical effectiveness [RR = 1.26, 95% CI (1.18, 1.35), p < .00001, I2  = 50%], time to defervescencer [MD = -1.45, 95% CI (-1.82, -1.07), p < .00001, I2  = 83%], disappearing time of cough [MD = -2.11, 95% CI (-2.98, -1.25), p < .00001, I2  = 93%], time of RT-PCR negativity [MD = -3.35, 95% CI (-4.74, -1.95), p < .00001, I2  = 92%], length of hospital stay [MD = -4.05, 95% CI (-5.24, -2.85), p < .00001, I2  = 91%], improvement in CT scan [RR = 1.22, 95% CI (1.17, 1.28), p < .00001, I2  = 46%], TCM syndrome score [MD = -3.95, 95% CI (-5.07, -2.82), p < .00001, I2  = 92%], disappearance rate of fever [RR = 1.23, 95% CI (1.10, 1.38), p < .00001, I2  = 85%], disappearance rate of cough [RR = 1.43, 95% CI (1.25, 1.63), p < .00001, I2  = 60%], level of CRP [MD = -9.23, 95% CI (-10.94, -7.52), p < .00001, I2  = 97%], and WBC [MD = -9.23, 95% CI (-10.94, -7.52), p < .00001, I2  = 97%]. There is no significant difference between ITCWM and WMT in the adverse reaction rate [RR = 0.85, 95% CI(0.71, 1.03), p = .10, I2  = 25%]. Our results showed evidence of clinical efficacy and safety benefit in COVID-19 patients treated with ITCWM. In spite of some limitations, the rapidly developing global pandemic warrants further high-quality and multicenter clinical studies to confirm the contribution of ITCWM.

Mechanical properties of gold nanowires prepared by nanoskiving approach.

The nanoskiving method based on nanocutting process is a new, low cost and easy way to machine nanowires. In this study, this technique is used to machine Au nanowires with different cutting directions and depths. Young's modulus and the yield strength of nanowires are then measured by an atomic force microscope-based three-point bending test. Results show that the Young's modulus of nanowires is independent of size and is not affected by cutting directions. However, the yield strength of nanowires machined by parallel cutting (NWs-b) is 42-64% higher than that machined by perpendicular cutting (NWs-a).

Meropenem selection induced overproduction of the intrinsic carbapenemase as well as phenotype divergence in Acinetobacter baumannii.

Acinetobacter baumannii 37662 is a carbapenem-susceptible isolate with blaOXA-51-like as the sole carbapenemase gene. Following selection with meropenem (MEM) at a subinhibitory concentration, two morphologically different mutants, designated 37662RM1 and 37662RM2, were obtained and characterised. Compared with the parent strain, resistant mutant 37662RM1 grew at a slower rate and had impaired capsule synthesis, whereas 37662RM2 grew fast and abolished capsule synthesis. In addition, the latter resistant mutant also lost pathogenicity but showed significantly enhanced biofilm formation. Transposition of the insertion sequence ISAba1 and formation of ISAba1-blaOXA-51-like was responsible for the upregulated expression of blaOXA-51-like. The blaOXA-51-like gene of A. baumannii 37662 is a close variant of blaOXA-138 and has been designated blaOXA-508. Overproduction of OXA-508 conferred major carbapenem resistance to these two mutants. Overall, these results indicate that a subinhibitory concentration of MEM can induce phenotype divergence together with carbapenem resistance in A. baumannii.

Repetition Priming Effects in Proficient Mandarin-Cantonese and Cantonese-Mandarin Bidialectals: An Event-Related Potential Study.

The present study adopted a repetition priming paradigm to investigate the bidialectal (bilingual) representation of speakers with different native dialects by event-related potential (ERP) technique. Proficient Mandarin-Cantonese and Cantonese-Mandarin bidialectals participated in the study. They were required to judge whether a word was a biological word or not, when the words (target word) were represented under four types of repetition priming conditions: Mandarin (prime)-Mandarin (target), Mandarin (prime)-Cantonese (target), Cantonese (prime)-Cantonese (target) and Cantonese (prime)-Mandarin (target). Results of reaction time and accuracy primarily indicated larger repetition priming effects in Mandarin-Mandarin and Cantonese-Cantonese (within-language) conditions than that in Mandarin-Cantonese and Cantonese-Mandarin (between-language) conditions. But more importantly, P200 and N400 mean amplitudes revealed distinct repetition priming effects between two types of participants. Specifically, both P200 and N400 indicated that the repetition priming effect in Mandarin-Mandarin condition was larger than that in Cantonese-Cantonese condition for Mandarin-Cantonese participants, whereas it was opposite for Cantonese-Mandarin participants. In addition, P200 also suggested opposite patterns of repetition priming effects in between-language priming conditions for two groups of participants. The repetition priming effect in Mandarin-Cantonese condition was larger than that in Cantonese-Mandarin condition for Mandarin-Cantonese participants, while for Cantonese-Mandarin participants, it was opposite (Mandarin-Cantonese < Cantonese-Mandarin). The results implied a clear asymmetric representation of two dialects for proficient bidialectals. They were further discussed in light of native dialect and language use frequency.

"Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.

Acinetobacter pittii 44551 was recovered from a patient with gout combined with tuberculosis and was found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM-44551 displayed high self-transferability across multiple bacterial species, while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii receipts. pNDM-44551 was a close variant of the previously characterized pNDM-BJ01, and the blaNDM-1 gene cluster was arranged sequentially as orfA, ISAba14, aphA6, ISAba125, blaNDM-1, bleMBL, ΔtrpF, dsbC, tnpR, and zeta. pOXA58-44551 was a repAci9-containing plasmid, and blaOXA-58 was embedded in a 372F-ISAba3-like-blaOXA-58-ISAba3 structure. The mobile genetic platforms of blaNDM-1 and blaOXA-58 herein showed some differences from their previously characterized variants. The production of NDM-1 in strain 44551 contributed the majority to its high resistance to carbapenems, while the blaOXA-58 stayed silent most likely due to the lack of an upstream promoter to drive its transcription. Increased surveillance of Acinetobacter co-harboring blaNDM-1 (active) and blaOXA-58 (either active or silent) is urgently needed.

[Treatment of acute injury of soft tissue around shoulder joint by exercise needling and electroacupuncture as main].

OBJECTIVE: To search for an effective method for treatment of acute injury of soft tissue around shoulder joint. METHODS: One hundred and twenty cases were randomly divided into an observation group, a control group 1 and a control group 2. The observation group were treated by exercise needling, electroacupuncture (EA) at Jianyu (LI 15), Jianliao (TE 14), Jianzhen (SI 9), etc. and TDP; the control group 1 were treated with EA at the same points as those in the observation group; the control group 2 were treated with oral administration of Fenbid slow-released capsules. The therapeutic effects were assessed after the first session of treatment, after one therapeutic course and one month after all the treatment by visual analog scale (VAS). RESULTS; The total effective rate of 100.0% and the cured-markedly effective rate of 95.0% in the observation group were better than 90.0%, 75.0% in the control group 1 and 70.0% and 45.0% in the control group 2 (P<0.01 or P<0.05); the VAS scores after the first treatment, after one therapeutic course and one month after all the treatment in the observation group were significantly lower than those in the two control groups (P<0.05). CONCLUSION: The combined treatment of exercise needling, EA and TDP is a good rehabilitation method for acute injury of soft tissue around shoulder joint.