The relationship between ethylene-induced autophagy and reactive oxygen species in Arabidopsis root cells during the early stages of waterlogging stress.

The response of plants to waterlogging stress is a complex process, with ethylene playing a crucial role as a signaling molecule. However, it remains unclear how ethylene is initially triggered in response to waterlogging stress when plants are continuously waterlogged for less than 12 hours. Here, we have shown that ethylene-induced autophagy leads to the degradation of damaged mitochondria (the main organelles producing reactive oxygen species (ROS)) to reduce ROS production during oxidative stress in Arabidopsis thaliana, which improves the survival rate of root cells in the early stages of waterlogging stress. Waterlogging stress activated ethylene-related genes, including ACO2, ACS2, ERF72, ERF73, and EIN3, and ethylene content of plants increased significantly within 24 h of continuous waterlogging. As stress duration increased, increased amounts of ROS accumulated in Arabidopsis thaliana roots, and the activity of antioxidant enzymes initially increased and then decreased. Concurrently, the level of ethylene-induced autophagy, which participates in antioxidant defense, is higher in wild-type plants than in the octuple acs mutant cs16651 (acs2-1/acs4-1/acs5-2/acs6-1/acs7-1/acs9-1/amiRacs8acs11). Exogenous application of 1-aminocyclopropanecarboxylic acid (ACC), resulted in a more pronounced manifestation of autophagy in the stele of Arabidopsis roots. Compared with the waterlogging treatment group or the ACC treatment group, the waterlogging + ACC treatment can induce autophagy to occur earlier and expand the autophagic range to the epidermis of Arabidopsis thaliana roots. Overall, our results provide insight into the important role of ethylene-induced autophagy in enhancing the antioxidative capacity of Arabidopsis thaliana during the early stages of waterlogging stress. Furthermore, we suggest ethylene as a potential candidate for mitigating the deleterious effects caused by waterlogging in Arabidopsis thaliana.

The opening of mitochondrial permeability transition pore (mPTP) and the inhibition of electron transfer chain (ETC) induce mitophagy in wheat roots under waterlogging stress.

Mitochondria are crucial for the regulation of intracellular energy metabolism, biosynthesis, and cell survival. And studies have demonstrated the role of mitochondria in oxidative stress-induced autophagy in plants. Previous studies found that waterlogging stress can induce the opening of mitochondrial permeability transition pore (mPTP) and the release of cytochrome c in endosperm cells, which proved that mPTP plays an important role in the programmed cell death of endosperm cells under waterlogging stress. This study investigated the effects of the opening of mPTP and the inhibition of ETC on mitophagy in wheat roots under waterlogging stress. The results showed that autophagy related genes in the mitochondria of wheat root cells could respond to waterlogging stress; waterlogging stress led to the degradation of the characteristic proteins cytochrome c and COXII in the mitochondria of root cells. With the prolongation of waterlogging time, the protein degradation degree and the occurrence of mitophagy gradually increased. Under waterlogging stress, exogenous mPTP opening inhibitor CsA inhibited mitophagy in root cells and alleviated mitophagy induced by flooding stress, while exogenous mPTP opening inducer CCCP induced mitophagy in root cells; exogenous mPTP opening inducer CCCP induced mitophagy in root cells. The electron transfer chain inhibitor antimycin A induces mitophagy in wheat root cells and exacerbates mitochondrial degradation. In conclusion, waterlogging stress led to the degradation of mitochondrial characteristic proteins and the occurrence of mitophagy in wheat root cells, and the opening of mPTP and the inhibition of ETC induced the occurrence of mitophagy.

MiR-7-5p/KLF4 signaling inhibits stemness and radioresistance in colorectal cancer.

Resistance to radiotherapy remains a major unmet clinical obstacle in the treatment of locally advanced rectal cancer. Cancer stem cells (CSCs) are considered to mediate tumor development and radioresistance. However, the role of CSCs in regulating resistance to radiotherapy in colorectal cancer (CRC) remains largely unknown. We established two radioresistant CRC cell lines, HCT116-R and RKO-R, using fractionated irradiation. Analysis using miRNA sequencing and quantitative real-time PCR confirmed lower levels of miR-7-5p in both of the radioresistant cells compared to their parental cells. Subsequently, we validated that miR-7-5p expression was decreased in cancerous tissues from radiotherapy-resistant rectal cancer patients. The Cancer Genome Atlas (TCGA) database analyses revealed that low miR-7-5p expression was significantly correlated with poor prognosis in CRC patients. Overexpression of miR-7-5p led to a rescue of radioresistance and an increase in radiation-induced apoptosis, and attenuated the stem cell-like properties in HCT116-R and RKO-R cells. Conversely, knocking down miR-7-5p in parental HCT116 and RKO cells suppressed the sensitivity to radiation treatment and enhance cancer cell stemness. Stemness-associated transcription factor KLF4 was demonstrated as a target of miR-7-5p. Rescue experiments revealed that miR-7-5p/KLF4 axis could induce radiosensitivity by regulating CSCs in colorectal cancer cells. Furthermore, we used CRC tumor tissues which exhibited resistance to neoadjuvant radiotherapy to establish a patient-derived xenograft (PDX) mouse model. Tail vein injection of magnetic nanoparticles carrying miR-7-5p mimics into the PDX mice significantly inhibited tumor growth with or without irradiation treatment in vivo. Our current studies not only demonstrate an anti-cancer function of miR-7-5p in regulating CSC properties and radiosensitivity in colorectal cancer, but also provide a novel potential strategy for delaying or reverse radiation resistance in preoperative radiotherapy of CRC patients.

Survival outcomes analysis according to mismatch repair status in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy.

Background: The predictive role of mismatch repair (MMR) status for survival outcomes and sensitivity in neoadjuvant chemoradiotherapy settings for patients with locally advanced rectal cancer (LARC) has been inconclusive. Methods: A retrospective cohort of patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) was recruited. After adjusting for baseline characteristics, we used propensity score matching to reduce the effect of potential confounding factors on MMR status. The primary analysis was based on overall survival as the more important endpoint. Results: This study included 269 patients. Patients with defective MMR (dMMR) were younger (58.5% vs. 60.0%, p=0.0274) and had lower body mass indices (p=0.0091), higher differentiation grades (p=0.0889), and more advanced rectal cancers (clinical T4 or T4b, p=0.0851; M1, p=0.0055) than those with proficient MMR (pMMR). However, propensity score-matched patients with dMMR (p=0.0013) exhibited superior overall survival, even in the M1 subgroup. More importantly, patients with proficient MMR who undergo early pathological downstaging, especially lymph node pathological downstaging, can achieve a prognosis similar to that of patients with dMMR. Conclusion: The clinical significance of this retrospective study mainly includes two points: (1) Data from our study confirmed that LARC patients with dMMR status had better overall survival rates after nCRT, even in the M1 subgroup. (2) Similar survival outcomes were observed in older and female patients with early lymph node pathological downstaging, regardless of dMMR or pMMR.

Chromosome-level genome of Entada phaseoloides provides insights into genome evolution and biosynthesis of triterpenoid saponins.

As a medicinal herbal plant, Entada phaseoloides has high levels of secondary metabolites, particularly triterpenoid saponins, which are important resources for scientific research and medical applications. However, the lack of a reference genome for this genus has limited research on its evolution and utilization of its medicinal potential. In this study, we report a chromosome-scale genome assembly for E. phaseoloides using Illumina, Nanopore long reads and high-throughput chromosome conformation capture technology. The assembled reference genome is 456.18 Mb (scaffold N50 = 30.9 Mb; contig N50 = 6.34 Mb) with 95.71% of the sequences anchored onto 14 pseudochromosomes. E. phaseoloides was estimated to have diverged from the Leguminosae lineage at ~72.0 million years ago. With the integration of transcriptomic and metabolomic data, gene expression patterns and metabolite profiling of E. phaseoloides were determined in different tissues. The pattern of gene expression and metabolic profile of the kernel were distinct from those of other tissues. Furthermore, the evolution of certain gene families involved in the biosynthesis of triterpenoid saponins and terpenes was analysed and offers new insights into the formation of these two metabolites. Four CYP genes, one UGT gene and related transcription factors were identified as candidate genes contributing to regulation of triterpenoid saponin biosynthesis. As the first high-quality assembled reference genome in the genus Entada, it will not only provide new information for the evolutionary study of this genus and conservation biology of E. phaseoloides but also lay a foundation for the formation and utilization of secondary metabolites in medicinal plants.

Iron phosphate hydroxide hydrate as a novel anode material for advanced aqueous full potassium-ion batteries.

The development of aqueous potassium-ion batteries is limited by the lack of suitable anode materials. Here, a novel anode material, iron phosphate hydroxide hydrate Fe1.19PO4(OH)0.18(H2O)0.3, was introduced and synthesized, which delivers considerable reversible capacities of 80 mA h g-1 at 0.05 A g-1. An aqueous full potassium-ion battery assembled with the K2Zn3(Fe(CN)6)2 cathode exhibits 80% capacity retention after 1000 cycles.

PIK3CA mutations-mediated downregulation of circLHFPL2 inhibits colorectal cancer progression via upregulating PTEN.

BACKGROUND: PIK3CA mutation and PTEN suppression lead to tumorigenesis and drug resistance in colorectal cancer (CRC). There is no research on the role of circular RNAs (circRNAs) in regulating PIK3CA mutation and MEK inhibitor resistance in CRC. METHODS: The expression of circLHFPL2 in PIK3CA-mutant and wild-type cells and tissues was quantified by RNA-sequencing and qRT-PCR. CCK-8 assay and colony formation assay were used to evaluate cell viability. Annexin V/PI staining was implemented to assess cell apoptosis. Luciferase assay, biotin-coupled microRNA capture, and RIP assay were used to validate the interaction among potential targets. Western blotting and qRT-PCR assays were used to evaluate the expression of involved targets. Xenograft tumor in a nude mouse model was used to explore the role of circRNAs in vivo. RESULTS: RNA sequencing defined downregulated expression of circLHFPL2 in both PIK3CAH1047R (HCT116) and PIK3CAE545K (DLD1) cells. CircLHFPL2 was also downregulated in PIK3CA-mutant CRC primary cells and tissues, which was correlated with poor prognosis. CircLHFPL2 was mainly localized in the cytoplasm and its downregulation was attributed to the PI3K/AKT signaling pathway activated by phosphorylating Foxo3a. CircLHFPL2 inhibited PI3KCA-Mut CRC progression both in vitro and in vivo. Furthermore, our work indicated that circLHFPL2 acts as a ceRNA to sponge miR-556-5p and miR-1322 in CRC cells and in turn modulate the expression of PTEN. Importantly, circLHFPL2 was able to overcome PIK3CA-mediated MEK inhibitor resistance in CRC cells. CONCLUSIONS: Downregulation of circLHFPL2 sustains the activation of the PI3K/AKT signaling pathway via a positive feedback loop in PIK3CA-mutant CRC. In addition, downregulation of circLHFPL2 leads to MEK inhibitor resistance in CRC. Therefore, targeting circLHFPL2 could be an effective approach for the treatment of CRC patients harboring oncogenic PIK3CA mutations.

Integrative Analysis of Metabolome and Transcriptome Identifies Potential Genes Involved in the Flavonoid Biosynthesis in Entada phaseoloides Stem.

Entada phaseoloides stem is known for its high medicinal benefits and ornamental value. Flavonoids are one of the main active constituents in E. phaseoloides stem. However, the regulatory mechanism of flavonoids accumulation in E. phaseoloides is lacking. Here, phytochemical compounds and transcripts from stems at different developmental stages in E. phaseoloides were investigated by metabolome and transcriptome analysis. The metabolite profiling of the oldest stem was obviously different from young and older stem tissues. A total of 198 flavonoids were detected, and flavones, flavonols, anthocyanins, isoflavones, and flavanones were the main subclasses. The metabolome data showed that the content of acacetin was significantly higher in the young stem and older stem than the oldest stem. Rutin and myricitrin showed significantly higher levels in the oldest stem. A total of 143 MYBs and 143 bHLHs were identified and classified in the RNA-seq data. Meanwhile, 34 flavonoid biosynthesis structural genes were identified. Based on the expression pattern of structural genes involved in flavonoid biosynthesis, it indicated that flavonol, anthocyanin, and proanthocyanin biosynthesis were first active during the development of E. phaseoloides stem, and the anthocyanin or proanthocyanin biosynthesis branch was dominant; the flavone biosynthesis branch was active at the late developmental stage of the stem. Through the correlation analysis of transcriptome and metabolome data, the potential candidate genes related to regulating flavonoid synthesis and transport were identified. Among them, the MYBs, bHLH, and TTG1 are coregulated biosynthesis of flavonols and structural genes, bHLH and transporter genes are coregulated biosynthesis of anthocyanins. In addition, the WDR gene TTG1-like (AN11) may regulate dihydrochalcones and flavonol biosynthesis in specific combinations with IIIb bHLH and R2R3-MYB proteins. Furthermore, the transport gene protein TRANSPARENT TESTA 12-like gene is positively regulated the accumulation of rutin, and the homolog of ABC transporter B family member gene is positively correlated with the content of flavone acacetin. This study offered candidate genes involved in flavonoid biosynthesis, information of flavonoid composition and characteristics of flavonoids accumulation, improved our understanding of the MYBs and bHLHs-related regulation networks of flavonoid biosynthesis in E. phaseoloides stem, and provided references for the metabolic engineering of flavonoid biosynthesis in E. phaseoloides stem.

Priority Management of Henle Trunk in Cranial-to-Caudal Approach for Laparoscopic Right Hemicolon Cancer Surgery.

This study aimed to compare the short-term clinical efficacy between prior and traditional approach of Henle trunk in laparoscopic right hemicolectomy (LRH) for right colon cancer. A total of 161 patients underwent LRH for right colon cancer between June 2018 and December 2020 by the same group of physicians. The prior approach of Henle trunk (priority group) was used in 82 patients and traditional approach in 79 (traditional group). The demographics and clinicopathological characteristics were recorded and retrospectively analyzed. As compared to the traditional group, the mean blood loss reduced significantly [73.84 ± 17.31 mL vs. 83.42 ± 30.16 mL; P = 0.001], the operation time was markedly shorter [151.35 ± 6.75 min vs. 159.13 ± 18.85 min; P = 0.014], and the intraoperative vascular injury rate was significantly lower [6.1% (5/82). vs. 17.7% (14/79); P = 0.022]. There were no significant differences in the postoperative complications, first exhaust time, first defecation time, drainage time, postoperative hospital stay, quality evaluation of surgical specimens and pathological findings between two groups. Our study shows that the priority management of Henle trunk in the LRH for right colon cancer is a safe and feasible procedure with less blood loss, shorter operation time and lower intraoperative vascular injury rate.

Up-regulated FNDC1 accelerates stemness and chemoradiation resistance in colorectal cancer cells.

Neoadjuvant chemoradiation (nCRT) followed by radical surgery is the preferred option for locally advanced colorectal cancer (CRC) treatment. However, chemo/radio-resistance remains a main obstacle in CRC therapy. In the study, we analyzed the mRNA expression profiling of CRC patients and revealed that the aberrant expression of fibronectin type III domain containing 1 (FNDC1) was associated with disease progression and poor prognosis in CRC. FNDC1 expression was consistently increased in multiple independent cohorts of CRC. Upregulated FNDC1 in pretreated primary tumor tissues predicted a poor response to nCRT, recurrence, and poor disease-free survival in nCRT-treated CRC patients. FNDC1 overexpression accelerated CRC cell survival on 5-FU or radiation treatment both in vitro and in vivo, whereas FNDC1 inhibition sensitized CRC cells to chemoradiation. In addition, FNDC1 accelerated stem cell-like properties of CRC cells. Furthermore, tumor tissues from non-responders exhibited higher activation of PI3K/Akt signaling than those from responders. FNDC1 depletion repressed 5-FU or irradiation-induced activation of PI3K/AKT in CRC cells. More importantly, pharmacological inhibition of PI3K/Akt signaling effectively decreased the effect of FNDC1 on chemoradiation resistance. Taken together, our study reveals the potential function of FNDC1 as a biomarker to predict nCRT sensitivity in CRC and a therapeutic target in CRC treatment.

Analgesic and neuroprotective effects of Baimai Ointment on diabetic peripheral neuropathy.

ETHNOPHARMACOLOGY RELEVANCE: Baimai (BM) ointment, a traditional Tibetan medicine, has been widely used to treat "white vein" disease, paralysis, hemiplegia and claudication caused by trauma, because of its great effects on muscle stretching and collateral activation. As one of the most terrible complications in diabetes patients, diabetes peripheral neuropathy (DPN) is mainly manifested as abnormal pain or numbness in extremities. However, whether BM ointment is a potential drug for DPN treatment is unclear. AIMS OF THE STUDY: The aim of this study was to investigate the therapeutic effects of BM on DPN in a high-fat diet/low-dose of streptozotocin induced type 2 diabetes rat model and explore underlying mechanisms. METHODS: The chemical components of BM were determined by high performance liquid chromatography (HPLC), and the possible targets and related pathways candidates involved in the effects of BM on DPN were predicted using network pharmacology methods. Next, the effects of different doses (1.5, 3.0 and 6.0 g/kg) of BM on physiological changes, pain behaviors, motor nerve conduction velocity (MNCV) in DPN rats were assessed and compared with placebo- and mecobalamine (Meco)-treated DPN controls. Then, the effects of BM on the expression of pain associated genes as well as the phosphorylation of PI3K/AKT and MAPKs pathways in DRG of DPN rats were examined. RESULTS: Through HPLC analysis, curcumin was identified as one of the primary contents of BM. The information from network pharmacology indicated a series of target candidates for BM including IL6, IL10, TNF, CCL2, CXCL12, EGF, VEGFA, BDNF, TGFß1 and TNF, as well as PI3K-AKT and MAPK signaling pathways. Topical treatment of BM significantly improved the hypersensitivity of mechanical and thermal pain, MNCV and the morphological changes and demyelination of sciatic nerve fibers, without affecting the body weight, serum metabolism or blood glucose. The up-regulated levels of neuropeptides Cgrp, Sst, Sp and chemokines Ccl2 and Ccl3 along with the abnormal expression of p-P38, p-ERK and p-AKT in the DRG of DPN rats were alleviated by BM application. CONCLUSION: BM ointment has great activities in relieving pain hypersensitivity, neuroprotecting peripheral nerves damage caused by DPN, which may be related to the inhibition of related neuropeptide (Cgrp, Sst, Sp) and chemokine (Ccl2, Ccl3) expression and the regulation of PI3K/AKT and MAPKs signaling pathways in DRG.

Natural variation in WHITE-CORE RATE 1 regulates redox homeostasis in rice endosperm to affect grain quality.

Grain chalkiness reduces the quality of rice (Oryza sativa) and is a highly undesirable trait for breeding and marketing. However, the underlying molecular cause of chalkiness remains largely unknown. Here, we cloned the F-box gene WHITE-CORE RATE 1 (WCR1), which negatively regulates grain chalkiness and improves grain quality in rice. A functional A/G variation in the promoter region of WCR1 generates the alleles WCR1A and WCR1G, which originated from tropical japonica and wild rice Oryza rufipogon, respectively. OsDOF17 is a transcriptional activator that binds to the AAAAG cis-element in the WCR1A promoter. WCR1 positively affects the transcription of the metallothionein gene MT2b and interacts with MT2b to inhibit its 26S proteasome-mediated degradation, leading to decreased reactive oxygen species production and delayed programmed cell death in rice endosperm. This, in turn, leads to reduced chalkiness. Our findings uncover a molecular mechanism underlying rice chalkiness and identify the promising natural variant WCR1A, with application potential for rice breeding.

AVL9 promotes colorectal carcinoma cell migration via regulating EGFR expression.

BACKGROUND: Despite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it's biological function and mechanism in CRC remain unclear. AIM: To investigate the biological role and mechanism of AVL9 in colorectal carcinoma. RESULTS: AVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration. CONCLUSION: These findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, suggesting a potential biomarker and treatment target for CRC.

Decreased E2F2 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Colorectal Cancer.

Growing evidence has revealed that the E2F family of transcription factor 2 (E2F2) participates in the tumorigenesis and progression of various tumors, but its role in colorectal cancer (CRC) remains largely unknown. Herein, the aim of our study was to investigate the exact role of E2F2 in CRC. The expression levels of E2F2 in CRC were appraised based on the Tumor Immune Estimate Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database. The results were further confirmed using CRC tumor tissues and normal controls by experimental assays including immunohistochemistry, qRT-PCR and western blot. The survival analysis of E2F2 in CRC was analyzed using PrognoScan database and TCGA data sets. In addition, the functional roles of E2F2 were examined by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. Our results illustrated that E2F2 was significantly downregulated in CRC samples. The low E2F2 expression in CRC was prominently correlated with N, M stage and pathological stage. Decreased E2F2 expression had an unfavorable overall survivial (OS), disease free survival (DFS), disease specific survival (DSS) and progress free interval (PFI). Multivariate cox regression showed E2F2 could be an independent prognostic factors of OS in CRC. Receiver operating characteristic (ROC) analysis showed that E2F2 may serve as a potential diagnostic biomarker for CRC patients. GSEA disclosed that E2F2 was probably involved in several pathways, including ATR pathway, ATM signalling pathway, mismatch repair, base excision repair, homologous recomibination, Fanconi Anemia pathway, multicancer invasiveness signature, and cancer stem cells. Moreover, E2F2 was significantly correlated with the infiltration level of Th2, aDC, Th17, NK CD56dim, T helper and pDC cells. The current study demonstrates that decreased E2F2 expression is closely associated with poor prognosis and immune cell infiltration in CRC, which can be a promising independent prognostic biomarker and potential treatment target for CRC.

Laparoscopic Natural Orifice Specimen Extraction Surgery versus Conventional Surgery in Colorectal Cancer: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study was to quantitatively synthesize data in randomized controlled trials (RCTs) of laparoscopic resection comparing natural orifice specimen extraction (NOSE) versus conventional laparoscopy (CL) in colorectal cancer. METHODS: We identified eligible RCTs by searching seven electronic databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, CQVIP, Wanfang, and Sinomed). Mean differences (MDs) between groups with 95% confidence intervals (CIs) were used for continuous outcomes. Event rate ratios (RRs) were also calculated with their 95% CIs. RESULTS: 1,569 citations were identified from electronic database as of June 2020, and finally, 21 RCTs involving 2,112 patients met the study eligibility criteria and were included. Compared to the CL group, NOSE had longer operation time (MD: 8.14 min, 95% CI: 3.02 to 13.25, and p < 0.01), less estimated blood loss (-10.64 ml, 95% CI: -14.92 to -6.36, and p < 0.01), less hospital stay after surgery (-2.21 days, 95% CI: -3.36 to -1.06, and p < 0.01), shorter time of gas passage after surgery (-0.58 days, 95% CI: -0.82 to -0.34, and p < 0.01), better pain score (-1.06, 95% CI: -3.74 to -0.37, and p < 0.01), and improved cosmetic scores (1.93, 95% CI: 0.77 to 3.10, p < 0.01). Rate ratios of total complications, infection, and incision infection all favored NOSE surgery, with RRs (95% CIs) of 0.81 (0.71 to 0.93), 0.34 (0.21 to 0.54), and 0.24 (0.12 to 0.51), respectively. CONCLUSION: This report appeared the first comprehensive meta-analysis of RCTs to synthesize data of laparoscopic resection with NOSE versus conventional laparoscopy. NOSE surgery seemed favorable with shorter hospital stay, less pain score, a shorter time to recover along with better cosmetic scores, and less postoperative complications.

TRIM22 inhibits the proliferation of gastric cancer cells through the Smad2 protein.

TRIM22 is involved in tumorigenesis and development, but its mechanism is not clear. In this study, we investigated the expression and biological role of TRIM22 in gastric cancer. We found that TRIM22 mRNA and protein expression was abnormally low in gastric cancer tissues and cells and correlated with tumor size and depth of invasion. Overexpression of TRIM22 significantly inhibited the proliferation, colony formation, and migration of gastric cancer cells and downregulated the expression of HSPA6. However, the HSPA6-siRNA complementation test showed that TRIM22 did not regulate cell proliferation through HSPA6. Furthermore, overexpression of TRIM22 downregulated the phosphorylation of Smad2 and Smad3. In addition, TRIM22 directly binds to Smad2, and overexpression of Smad2 can reverse the inhibition of cell proliferation and migration induced by TRIM22. In vivo, overexpression of TRIM22 significantly inhibited the growth of subcutaneous xenografts in nude mice. Our study indicates that TRIM22 has an important role in the development of gastric cancer and may inhibit the proliferation of gastric cancer cells through Smad2.

Low Concentration DMF/H2O Hybrid Electrolyte: A New Opportunity for Anode Materials in Aqueous Potassium-Ion Batteries.

Superconcentrated "water-in-salt" electrolytes have greatly widened the electrochemical stable window (ESW) of aqueous electrolytes, but they also generate new problems, including high costs, high viscosity, and low conductivity. Here we report a 2 m low concentration electrolyte using an N,N-dimethylformamide/water (DMF/H2O) hybrid solvent, which provides a wider ESW (2.89 V) than an aqueous electrolyte (2.66 V) and presents nonflammability, high conductivity, and low viscosity characteristics. In 2 m DMF/H2O hybrid electrolyte, the LUMO energy of the DMF solvent (-0.00931 a.u.) is lower than that of H2O (-0.00735 a.u.), which could effectively promote the degradation of FSI- and lead to stable solid electrolyte interphase formation. As a result, the electrochemical reversibility and cyclability of the KTi2(PO4)3@C (KTP@C) anode in the aqueous electrolyte have been significantly enhanced with the help of DMF addition. Moreover, the K2Zn3(Fe(CN)6)2 (KZnHCF)//KTP@C full potassium-ion battery exhibits highly efficient stability and rate capability with a long cycle performance over 10 000 cycles and delivers a specific discharge capacity of 33 mAh g-1 at a high current density of 20 A g-1. Low concentrations of DMF/H2O hybrid electrolytes can inhibit the hydrogen evolution reaction of aqueous electrolytes, providing more opportunities for the practical application of electrode materials. Not limited to DMF solvent, mixing organic and aqueous solvents will provide more available options and perspectives for improving the energy density and long cycle performance of the aqueous metal-ion battery.

Short-term waterlogging-induced autophagy in root cells of wheat can inhibit programmed cell death.

Autophagy is a pathway for the degradation of cytoplasmic components in eukaryotes. In wheat, the mechanism by which autophagy regulates programmed cell death (PCD) is unknown. Here, we demonstrated that short-term waterlogging-induced autophagy inhibited PCD in root cells of wheat. The waterlogging-tolerant wheat cultivar Huamai 8 and the waterlogging-sensitive wheat cultivar Huamai 9 were used as experimental materials, and their roots were waterlogged for 0-48 h. Waterlogging stress increased the number of autophagic structures, the expression levels of autophagy-related genes (TaATG), and the occurrence of PCD in root cells. PCD manifested as morphological changes in the cell nucleus, significant enhancement of DNA laddering bands, and increases in caspase-like protease activity and the expression levels of metacaspase genes. The autophagy promoter rapamycin (RAPA) reduced PCD levels, whereas the autophagy inhibitor 3-methyladenine (3-MA) enhanced them. The expression levels of TaATG genes and the number of autophagic structures were lower in cortex cells than in stele cells, but the levels of PCD were higher in cortex cells. The number of autophagic structures was greater in Huamai 8 than in Huamai 9, but the levels of PCD were lower. In summary, our results showed that short-term waterlogging induced autophagy which could inhibit PCD. Mechanisms of response to waterlogging stress differed between cortex and stele cells and between two wheat cultivars of contrasting waterlogging tolerance.