Chemoresistance and tumor relapse are the leading cause of deaths in bladder cancer patients. Bladder cancer stem cells (BCSCs) have been reported to contribute to these pathologic properties. ...However, the molecular mechanisms underlying their self-renewal and chemoresistance remain largely unknown. In the current study, a novel lncRNA termed Low expressed in Bladder Cancer Stem cells (
) has been identified and explored in BCSCs.
Firstly, we establish BCSCs model and explore the BCSCs-associated lncRNAs by transcriptome microarray. The expression and clinical features of
are analyzed in three independent large-scale cohorts. The functional role and mechanism of
are further investigated by gain- and loss-of-function assays
and
.
is significantly downregulated in BCSCs and cancer tissues, and correlates with tumor grade, chemotherapy response, and prognosis. Moreover,
markedly inhibits self-renewal, chemoresistance, and tumor initiation of BCSCs both
and
. Mechanistically,
directly binds to heterogeneous nuclear ribonucleoprotein K (hnRNPK) and enhancer of zeste homolog 2 (EZH2), and serves as a scaffold to induce the formation of this complex to repress SRY-box 2 (SOX2) transcription via mediating histone H3 lysine 27 tri-methylation. SOX2 is essential for self-renewal and chemoresistance of BCSCs, and correlates with the clinical severity and prognosis of bladder cancer patients.
As a novel regulator,
plays an important tumor-suppressor role in BCSCs' self-renewal and chemoresistance, contributing to weak tumorigenesis and enhanced chemosensitivity. The
-hnRNPK-EZH2-SOX2 regulatory axis may represent a therapeutic target for clinical intervention in chemoresistant bladder cancer.
This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury.
This retrospective study included 45 patients with CPN injuries ...treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function.
Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661-1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575-0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582-0.953, P = 0.025) and 0.853 (95% CI = 0.693-1.000, P = 0.001), respectively.
Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.
A novel electrocatalytic system was developed to realize one-pot conversion of organic pollutants into liquid fuels such as methanol (CH3OH) and ethanol (C2H5OH). The process combines the catalytic ...oxidation of organic pollutants with electrocatalytic reduction of CO2. We first coupled the electrocatalytic process with SO4•−-based advanced oxidation processes (AOPs) for the degradation of 4-nitrophenol (4-NP) using a 3D-hexagonal Co3O4 anode. In this step, 4-NP was mineralized to CO2, and then the CO2 was converted to CH3OH and C2H5OH by electrocatalytic reduction using a flower-like CuO cathode. The experimental results show the destruction of 4-NP (60 mL, 10 mg/L) can be as high as 99%. In addition, the yields of CH3OH and C2H5OH were 98.29 μmol/L and 40.95 μmol/L, respectively, which represents a conversion of 41.8% of 4-NP into liquid fuels; the electron efficiency was 73.1%. In addition, we found that 3D-hexagonal arrays of Co3O4 with different morphologies can be obtained by adding different amounts of urea. We also investigated the formation mechanism of novel 3D-hexagonal Co3O4 arrays for the first time. A mechanism was proposed to explain the electrocatalytic steps involved in the conversion of 4-NP to CH3OH and C2H5OH and the synergetic effects between AOPs and electrocatalysis.
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•Organic pollutants to hydrocarbons was fulfilled in one electrocatalytic system.•SO4.•− for high-efficient degradation of organic pollutants was proposed.•3D-hexagonal Co3O4 array was prepared and formation mechanism was proposed.•A mechanism was proposed to explain the electrocatalytic steps.
In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates ...cancer cell apoptosis through several post‐translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2‐induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle–related and apoptosis‐related genes in cisplatin‐stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1‐mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.
The Cu(II) and Ni(II) complexes self-assembled from a novel salamo-like ligand H2L containing double terminal pyridine groups, Cu(LH)NO3⋅CH3CH2OH and {Ni(L)}2n·nC5H5N⋅nCH3COCH3 were designed and ...synthesized. The Cu(II) atom is located at the N2O2 cavity of the deprotonation ligand (L)2− moiety, but the N atoms of the terminal pyridine groups of the ligand (L)2− moiety is not involved in the coordination, and forms a four-coordinated twisted quadrilateral geometry. While the Ni(II) atom (Ni1 or Ni2) is sited in the N2O2 cavity of the deprotonation ligand (L)2− moiety and forms a plane, the terminal pyridine N atoms from the two adjacent Ni(L) moieties also coordinated with the Ni(II) atom in the axial positions to form a slightly distorted octahedral geometry with six-coordination. The benzene and pyridine rings of the ligand (L)2− moiety are rotated and create an angle, result to form a chiral MOFs using an achiral ligand (L)2− moiety.
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•Containing double terminal pyridine groups novel salamo-like ligand was synthesized.•The structurally different Cu(II) and Ni(II) complexes were self-assembled.•The Cu(II) and Ni(II) complexes have huge structural differences.•Compared with the Cu(Ⅱ) complex, the Ni(Ⅱ) complex has better thermal stability.
A novel structurally characterized salamo-like ligand H2L contained double terminal pyridine groups was designed and synthesized. The single crystals of the Cu(II) and Ni(II) complexes are grown up through coordination of H2L with Cu(II) and Ni(II) ions, respectively, determined as Cu(LH)NO3⋅CH3CH2OH and {Ni(L)}2n·n3C5H5N·nCH3COCH3. The Cu(II) atom is located at the N2O2 cavity of the deprotonation ligand (L)2− moiety, but the N atoms of the terminal pyridine groups of the ligand (L)2− moiety is not involved in the coordination, and forms a four-coordinated twisted quadrilateral geometry. While the Ni(II) atom (Ni1 or Ni2) is sited in the N2O2 cavity of the deprotonation ligand (L)2− moiety and forms a plane, the terminal pyridine N atoms from the two adjacent Ni(L) moieties also coordinated with the Ni(II) atom in the axial positions to form a slightly distorted octahedral geometry with six-coordination. In the formation of MOFs, the benzene and pyridine rings of the ligand (L)2− moiety are rotated and create an angle, result to form a chiral MOFs using an achiral ligand (L)2− moiety. View of MOFs in the C direction, the Ni(II) complex has four different size of apertures in its structure, and presences a large amount of protonic hydrogen. Spectroscopic analyses of H2L and its Cu(II) and Ni(II) complexes are performed using IR, UV–Vis and fluorescence spectroscopy. Compared with the Cu(II) complex, the Ni(II) complex has better thermal stability. The magnetic analyses were also carried out. Hirshfeld surfaces analyses are carried out to analyze various short-range interactions in H2L and its Cu(II) complex.
The hot compressive deformation behaviors of a typical Ni-based superalloy are investigated over wide ranges of forming temperature and strain rate. Based on the experimental data, the efficiencies ...of power dissipation and instability parameters are evaluated and processing maps are developed to optimize the hot working processing. The microstructures of the studied Ni-based superalloy are analyzed to correlate with the processing maps. It can be found that the flow stress is sensitive to the forming temperature and strain rate. With the increase of forming temperature or the decrease of strain rate, the flow stress significantly decreases. The changes of instability domains may be related to the adiabatic shear bands and the evolution of δ phase(Ni3Nb) during the hot formation. Three optimum hot deformation domains for different forming processes (ingot cogging, conventional die forging and isothermal die forging) are identified, which are validated by the microstructural features and adiabatic shear bands. The optimum window for the ingot cogging processing is identified as the temperature range of 1010–1040°C and strain rate range of 0.1–1s−1. The temperature range of 980–1040°C and strain rate range of 0.01–0.1s−1can be selected for the conventional die forging. Additionally, the optimum hot working domain for the isothermal die forging is 1010–1040°C and near/below 0.001s−1.
Mitochondrial fission regulator 2 (MTFR2) was involved in the progression and development of various cancers. However, the relationship between MTFR2 with lung adenocarcinoma (LUAD) had not been ...reported. Herein, this study analyzed the clinical significance and potential mechanisms of MTFR2 in LUAD via bioinformatics tools.
We found that the level of MTFR2 was increased, and correlated with sex, age, smoking history, neoplasm staging, histological subtype and TP53 mutation status in LUAD patients. Kaplan-Meier survival analysis showed LUAD patients with increased MTFR2 had a poor prognosis. In addition, univariate COX regression analysis showed neoplasm staging, T stage, distant metastasis and MTFR2 level were risk factors for the prognosis of LUAD. A total of 1127 genes were coexpressed with MTFR2, including 840 positive and 208 negative related genes. KEGG and GSEA found that MTFR2 participated in the progression of LUAD by affecting cell cycle, DNA replication, homologous recombination, p53 signaling pathway and other mechanisms. The top 10 coexpressed genes, namely CDK1, CDC20, CCNB1, PLK1, CCNA2, AURKB, CCNB2, BUB1B, MAD2L1 and BUB1 were highly expressed, and were associated with poor prognosis in LUAD.
Consequently, we elucidated MTFR2 was a biomarker for diagnosis and poor prognosis in LUAD, and might participate in the progression of LUAD via affecting cell cycle, DNA replication, homologous recombination and p53 signaling pathway.
Abstract
BACKGROUND
The contralateral C7 transfer has been used for the treatment of brachial plexus root avulsion since 1986, and several modifications of this surgery have been described. Previous ...trial has verified the safety and effectiveness of the contralateral C7 to C7 cross nerve transfer for patients with longstanding spastic paralysis due to cerebral injuries, including stroke, traumatic brain injury, or cerebral palsy. However, the procedures for the surgery were not introduced in detail, with only rough descriptions.
OBJECTIVE
To introduce and promote the Xu's CC7 procedure (contralateral C7 to C7 cross nerve transfer through a trans longus colli, prespinal route).
METHODS
The renewed procedures were elaborated step by step, and the tips and tricks were clarified by case illustration in detail. Briefly, a modified trans longus colli, prespinal route was created, allowing the displaced C7 nerve to pass through the channel safely at the shortest distance.
RESULTS
Tension-free anastomosis of the bilateral C7 nerves was achieved via the Xu's CC7 procedure with less surgical trauma while reducing the surgery time, postoperative recovery time, and nerve regeneration time.
CONCLUSION
The Xu's CC7 procedure is a safer and more efficient technique for contralateral C7 to C7 cross nerve transfer. The detailed description in this article provides meaningful information for surgeons interested in the procedure.
Hot tensile tests are performed on an Al-Zn-Mg-Cu alloy at larger temperature and strain rate ranges. The influences of deformation parameters and stress triaxiality on hot tensile fracture ...characteristics, fracture mechanisms and microstructural evolution are discussed. It is found that the maximum tensile load increases with raising stress triaxiality. The fracture strain rises with increasing strain rate or decreasing stress triaxiality. When the deformation temperature is raised, the fracture strain firstly increases and then decreases. Dynamic recovery (DRV) is the main softening mechanism. At low strain rates or high deformation temperatures, the partial dynamic recrystallization (DRX) behavior occurs, and continuous dynamic recrystallization (CDRX) is the main DRX mode. The dominant fracture mechanism is the coalescence of micro-voids at the tested deformation conditions. Due to the occurrence of DRX, the intergranular fracture also occurs at low strain rates or high deformation temperatures. The low strain rate or high stress triaxiality easily induces the appearance of micro-voids, which accelerate the fracture failure.
•Effects of deformation conditions and stress triaxiality on hot tensile fracture features and microstructures are studied.•The fracture strain rises with increasing strain rate or decreasing stress triaxiality.•At low strain rates or high temperatures, continuous dynamic recrystallization (CDRX) is the main DRX mode.•Dominant fracture mechanism is the coalescence of micro-voids at the tested deformation conditions.•Low strain rate or high stress triaxiality easily induces the appearance of micro-voids, accelerating the fracture.
Hot compressive deformation behaviors of the aged nickel-based superalloy are studied under the deformation temperature range of 920–1040°C and strain rate range of 0.001–1s−1. Based on the ...experimental data, the processing maps are developed and correlated with the deformed microstructures of the studied nickel-based superalloy. The effects of initial aging time on the processing map and microstructures are discussed in detail. It is found that the processing map and microstructures are sensitive to the initial aging time. When the initial aging time is shorter than 12h, the spherical and short needle-shaped δ phases (Ni3Nb) can stimulate the occurrence of dynamic recrystallization and improve the hot workability, as well as decrease the final forging temperature of the studied nickel-based superalloy. However, when the initial aging time is increased to 24h, the excessive long needle-shaped δ phases appear and become the potential locations of wedge cracking, which easily leads to flow instability during hot deformation. The aged superalloy under 900°C for 9h or 12h is suitable for the hammer forging process. The optimum deformation parameters for the hammer forging process are 1010–1040°C and 0.1–1s−1. The aged superalloy under 900°C for 9h can be used for the conventional die forging. Furthermore, the forging temperature should be controlled in the range of 980–1040°C, and the strain rate should be lower than 0.1s−1. The solution-treated superalloy or the aged superalloy under 900°C for 6h or 9h is suitable for the isothermal die forging, and the optimum hot deformation parameters is 980–1040°C and near 0.001s−1.
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