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Background Copper homeostasis is associated with malignant biological behavior in various tumors. The excessive accumulation of copper can induce tumor death, which is named cuproptosis, and it is also closely related to tumor progression and the formation of the immune microenvironment. However, the associations of cuproptosis with glioblastoma (GBM) prognosis and microenvironment construction are poorly understood. Method First, TCGA and GEO (GSE83300, GSE74187) merged datasets were used to analyze the association of cuproptosis-related genes (CRGs) with GBM. Then, we performed cluster analysis of CRGs in GBM from the GEO (GSE83300, GSE74187) and TCGA merged datasets. Subsequently, the prognostic risk model was constructed by least absolute shrinkage and selection operator (LASSO) according to gene expression features in CRG clusters. Next, we performed a series of in-depth analyses, including tumor mutational burden (TMB) analysis, cluster analysis, and GBM IDH status prediction. Finally, RARRES2 was identified as a target gene for GBM treatment, especially IDH wild-type GBM. In addition, we further analyzed the correlation of CRG clusters and RARRES2 expression with the GBM immune microenvironment by ESTIMATE and CIBERSORT analyses. In vitro experiments were conducted to demonstrate that targeting RARRES2 inhibits glioblastoma progression and macrophage infiltration, particularly IDH wild-type GBM. Results In the present study, we demonstrated that the CRG cluster was closely related to GBM prognosis and immune cell infiltration. Moreover, the prognostic risk model constructed with the three genes (MMP19, G0S2, RARRES2) associated with the CRG clusters could well evaluate the prognosis and immune cell infiltration in GBM. Subsequently, after further analyzing the tumor mutational burden (TMB) in GBM, we confirmed that RARRES2 in the prognostic risk model could be used as a crucial gene signature to predict the prognosis, immune cell infiltration and IDH status of GBM patients. Conclusion This study fully revealed the potential clinical impact of CRGs on GBM prognosis and the microenvironment, and determined the effect of the crucial gene (RARRES2) on the prognosis and tumor microenvironment construction of GBM, meanwhile, our study also revealed over-expressed RARRES2 is related to the IDH satus of GBM, which provides a novel strategy for the treatment of GBM, particularly IDH wild-type GBM.

The sluggish kinetics of both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) generate the large overpotential in water electrolysis and thus high-cost hydrogen production. Here, multidimensional nanoporous interpenetrating-phase FeNiZn alloy and FeNi3 intermetallic heterostructure is in situ constructed on NiFe foam (FeNiZn/FeNi3@NiFe) by dealloying protocol. Coupling with the eminent synergism among specific constituents and the highly efficient mass transport from integrated porous backbone, FeNiZn/FeNi3@NiFe depicts exceptional bifunctional activities for water splitting with extremely low overpotentials toward OER and HER (η1000 = 367/245 mV) as well as the robust durability during the 400 h testing in alkaline solution. The as-built water electrolyzer with FeNiZn/FeNi3@NiFe as both anode and cathode exhibits record-high performances for sustainable hydrogen output in terms of much lower cell voltage of 1.759 and 1.919 V to deliver the current density of 500 and 1000 mA cm−2 as well long working lives. Density functional theory calculations disclose that the interface interaction between FeNiZn alloy and FeNi3 intermetallic generates the modulated electron structure state and optimized intermediate chemisorption, thus diminishing the energy barriers for hydrogen production in water splitting. With the merits of fine performances, scalable fabrication, and low cost, FeNiZn/FeNi3@NiFe holds prospective application potential as the bifunctional electrocatalyst for water splitting."Image missing"

Background Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. Methods We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People’s Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC’s amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. Results (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p L=3.916, p R=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p R=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively. Conclusion The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.

The harmonious functioning of growth plate chondrocytes is crucial for skeletogenesis. These cells rely on an appropriate intensity of glycolysis to maintain survival and function in an avascular environment, but the underlying mechanism is poorly understood. Here we show that Hnrnpk orchestrates growth plate development by maintaining the appropriate intensity of glycolysis in chondrocytes. Ablating Hnrnpk causes the occurrence of dwarfism, exhibiting damaged survival and premature differentiation of growth plate chondrocytes. Furthermore, Hnrnpk deficiency results in enhanced transdifferentiation of hypertrophic chondrocytes and increased bone mass. In terms of mechanism, Hnrnpk binds to Hif1a mRNA and promotes its degradation. Deleting Hnrnpk upregulates the expression of Hif1α, leading to the increased expression of downstream glycolytic enzymes and then exorbitant glycolysis. Our study establishes an essential role of Hnrnpk in orchestrating the survival and differentiation of chondrocytes, regulating the Hif1α-glycolysis axis through a post-transcriptional mechanism during growth plate development.

Background People with sleep problems are more likely to have mental disorders. This study aimed to assess the effect of insomnia on the prognosis of patients with major depressive disorder (MDD). Methods We divided the patients into three groups according to the Insomnia Severity Index (ISI) scores. In addition, we compared the results of the Hamilton Depression Scale (HAMD) and Symptom Checklist-90 (SCL-90) scores. We evaluated the effect of insomnia at the 2nd, 4th, and 8th-week follow-up on the prognosis of MDD. Results Fifty-five patients between 19 and 58 years old, with a diagnosis of MDD via the Structured Clinical Interview for the Diagnostic and Statistical Manual-5 (DSM-5). The ISI scores of the moderate and severe group decreased significantly (P Conclusions This study was inspired to assess insomnia as a comorbid disorder for patients with MDD, which may bring poor treatment consequences.

Electrocatalytic water splitting via hydrogen evolution reaction (HER) represents one of promising strategies to gain hydrogen energy. In current work, self-supporting Co0.85Se nanosheets network anchored on Co plate (Co0.85Se NSs@Co) is fabricated by employing easily tailorable Co metal plate as the source conductive substrate. The scalable dealloying and hydrothermal selenization strategy was employed to build one layer of three dimensional interlinking Co0.85Se nanosheets network on the surface of Co plate. Benefiting from bulky integrated architecture and rich active sites, the as-made Co0.85Se NSs@Co exhibits superior electrocatalytic activity and long-term catalytic durability toward HER. It only requires lower overpotentials of 121 and 162 mV to drive the current density of 10 mA·cm−2 for hydrogen evolution in 0.5 M H2SO4 and 1 M KOH solution. Especially, no evident activity decay occurs upon 1,500 cycles or continuous test for 20 h at 10 mA·cm−2 in both acidic and alkaline electrolytes. With the merits of exceptional performances, scalable production, and low cost, the self-supporting Co0.85Se NSs@Co holds prospective application potential as stable and binder-free electrocatalysts for hydrogen generation in a wide range of electrolyte.

Hollow NiCoSex (H-NiCoSex) nanospheres encapsulated with carbon shell were prepared via one-step easy solvothermal method followed by the carbon coating process. H-NiCoSex@C has large interior void with the uniform dimension around 350 nm and the thickness of carbon shell around 20–30 nm. Coupling with the large interior void as well as robust protective carbon shell, H-NiCoSex@C can retain the reversible capacity of 805.6 mAh·g−1 after 100 cycles at 200 mA·g−1. In particular, H-NiCoSex@C delivers large reversible capacity of 1532.2 mAh·g−1 upon cycling for 1000 loops at 1000 mA·g−1 with the capacity retention as high as 128.2% upon long period of activation. Even at the high rate of 3000 mA·g−1, its specific capacity still retains up to 659.3 mAh·g−1. The superior lithium storage performances for H-NiCoSex@C profit from its robust hollow core-shell structure as well as enhanced electrical conductivity and ion transport.

BackgroundLong bones of limbs are formed through endochondral bone formation, which depends on the coordinated development of growth plates. Our previous studies have demonstrated that dysfunction of mitogen-activated protein kinase 7 (MAPK7) can cause skeletal dysplasia. However, little is known about the role of MAPK7 in the regulation of proliferation and differentiation of chondrocytes during growth plate development.ResultsAblation of MAPK7 expression in chondrocytes led to growth restriction, short limbs and bone mass loss in postnatal mice. Histological studies revealed that MAPK7 deficiency increased the apoptosis and decreased the proliferation of chondrocytes in the center of the proliferative layer, where the most highly hypoxic chondrocytes are located. Accordingly, hypertrophic differentiation markers were downregulated in the central hypertrophic layer, beneath the site where abnormal apoptosis was observed. Simultaneously, we demonstrated that hypoxic adaptation and hypoxia-induced activation of hypoxia-inducible factor 1 subunit α (HIF1α) were impaired when MAPK7 could not be activated normally in primary chondrocytes. Concomitantly, vascular invasion into epiphyseal cartilage was inhibited whenMapk7was deleted.ConclusionsWe demonstrated that MAPK7 is necessary for maintaining proliferation, survival, and differentiation of chondrocytes during postnatal growth plate development, possibly through modulating HIF1α signaling for adaptation to hypoxia. These results indicate that MAPK7 signaling might be a target for treatment of chondrodysplasia.

A superior NADH sensing platform was constructed based on porous PtAg nanoshells supported on reduced graphene oxide (PtAg/rGO) in the absence of any enzymes and redox mediators. The PtAg/rGO composite was prepared via one-step reduction combined with galvanic replacement reaction. The as-made PtAg/rGO assembles multiple structural advantages of coherent conductive matrix, rich electroactive sites, and high specific surface area, accompanied by the unique alloying effect. The PtAg/rGO possesses adequate active reaction sites and fluent electron transport pathway towards the electrocatalytic NADH oxidation, thus presenting significantly increased oxidation current and negative shift of 330 mV in applied potential relative to the bare GCE. By virtues of the outstanding electrocatalytic activity, PtAg/rGO exhibits effective amperometric detection of NADH at 0.15 V within a wide linear concentration range of 2–2378 μM, a high sensitivity of 92.62 μA mM−1 cm−2, low detection limit of 0.2 μM, and long-term detection over 2500 s. Moreover, the as-constructed biosensors can achieve accurate NADH detection in human serum samples, indicating its promising application feasibility in fundamental and clinic research.

A rare case of a 15-year-old male patient with neuromuscular scoliosis with forced vital capacity (FVC) below 30%, who went through a successful surgery without any pulmonary complications, is reported herein. The patient had obvious asymmetric shoulders and poor exercise tolerance. The Cobb's angle of the main thoracic curve was 62.8°, and FVC in sitting position was 18% of predictive value. After skull traction and pulmonary rehabilitation, the FVC was still below 30%, and he finally went through surgery under this serious condition. By early pulmonary rehabilitation using home ventilator, he successfully recovered without any pulmonary complications. The patient had complete symptom remission and no deterioration of Cobb's angle was found during follow-up.

Multimodal nanoporous PtCu flowers (np-PtCu) were prepared via a two-step dealloying strategy under mild conditions. The np-PtCu alloy possesses an interconnected flower-like network skeleton with multiscale pore distribution. This material was placed on a glassy carbon electrode where it shows outstanding detection performance towards hydrogen peroxide and glucose in near-neutral pH solutions. It can be attributed to the specific structure in terms of interconnected nanoscaled ligaments, rich pore openings and a synergistic alloying effect. Figures of merit for detection H2O2 assay include (a) a working voltage of 0.7 V (vs. the reversible hydrogen electrode); (b) a wide linear response range (from 0.01 to 1.7 mM), and (c) a low detection limit (0.1 μM). The respective data for the glucose assay are (a) 0.4 V, (b) 0.01–2.0 mM, and (c) 0.1 μM. The method is not interfered in the presence of common concentrations of dopamine, acetaminophen and ascorbic acid.

Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage. Collagen type II (COL2A1) was previously considered to be only a structural component of the cartilage matrix, but recently, it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy. However, the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear. In our study, a Col2a1 p.Gly1170Ser mutant mouse model was constructed, and Col2a1 loss was demonstrated in homozygotes. Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein (BMP)-SMAD1 pathway. Upon interacting with COL2A1, integrin β1 (ITGB1), the major receptor for COL2A1, competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import. COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and, through ERK1/2-SMAD1 interaction, it further repressed SMAD1 activation, thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy. Moreover, COL2A1 expression was downregulated, while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage. Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression., Breaking a destructive cycle A signaling feedback loop that contributes to cartilage degeneration may offer a fruitful target for the treatment of osteoarthritis. During the early stages of this disorder, cartilage-forming chondrocytes undergo a process of expansion known as hypertrophy, after which they die and are replaced by calcium. Researchers led by Peiqiang Su and Dongsheng Huang of Sun Yat-sen University have demonstrated that COL2A1, an important structural protein, represents an important safeguard against hypertrophy. COL2A1 helps maintain chondrocytes in their normal, healthy state, but Su and Huang showed that signaling factors produced during cartilage repair can reduce COL2A1 levels. This in turn accelerates hypertrophy, promoting further depletion of COL2A1 and ultimately leading to full-blown osteoarthritis. Drugs that break this cycle and preserve COL2A1 could thus help protect endangered joints before the damage becomes severe.

Nanoporous (NP) Si/Cu composites are fabricated by means of alloy refining followed by facile electroless dealloying in mild conditions. NP-Si/Cu composites with a three-dimensional porous network nanoarchitecture with different Cu contents are obtained by changing the feeding ratio of alloy precursors. Owing to the rich porosity and integration of conductive Cu into a nanoporous Si backbone, the NP-Si85Cu15 composite exhibits modified conductivity and reduced volumetric expansion/fracture during repeated charging-discharging processes in lithium-ion batteries (LIBs), thus exhibiting much higher cycling reversibility than NP-Si92Cu8 and pure NP-Si. With the advantages of unique performance and easy preparation, NP-Si/Cu composite has potential for application as an advanced anode material for LIBs.

A hierarchical nanoporous PtCu alloy was fabricated by two-step dealloying of a PtCuAl precursor alloy followed by annealing. The new alloy possesses interconnected hierarchical network architecture with bimodal distributions of ligaments and pores. It exhibits high electrochemical activity towards the oxidation of ascorbic acid (AA), dopamine (DA), and uric acid (UA) at working potentials of 0.32, 0.47 and 0.61 V (vs. a mercury sulfate reference electrode), respectively. The new alloy was placed on a glassy carbon electrode and then displayed a wide linear response to AA, DA, and UA in the concentration ranges from 25 to 800 μM, 4 to 20 μM, and 10 to 70 μM, respectively. The lower detection limits are 17.5 μM, 2.8 µM and 5.7 μM at an S/N ratio of 3.

Octahydroxyl-terminated and hexadecahydroxyl-terminated hyperbranched polyesters (HPE-8 and HPE-16) were synthesized from 2,2-dimethylol propionic acid and 1,4-butanediol. The hyperbranched waterborne polyurethane (HWPU) thickeners containing different branching structure and length of hydrophilic chain were prepared with hexamethylene diisocyanate, polyethylene glycol (PEG), cetyl alcohol, and HPE. The structures of HPE and HWPU were characterized by Fourier transform infrared spectra and nuclear magnetic resonance (1H NMR and 13C NMR). The rheological properties of polyurethane emulsion thickened by HWPU were measured using Brookfield LVDV-III rheometer, and the effects of HPE structure and PEG molecular weight on the thickening property of HWPU were studied. The results showed that HWPU with HPE branching number of 8 and PEG molecular weight of 4000 exhibited an excellent thickening effect in the aqueous polyurethane emulsion.

The striped flea beetle, Phyllotreta striolata (F.) (Coleoptera: Chrysomelidae), is an economically important pest on crucifer vegetables worldwide. Twenty isolates of entomopathogenic nematodes (EPNs) (Rhabditida: Steinernematidae and Heterorhabditidae) were evaluated against soil-dwelling stages of the flea beetle in the laboratory. The corrected mortalities and reproduction rates at a concentration of 36 infective juveniles (IJs) cm−2 surface area of sand against third instars of the pest greatly differed among the tested isolates, ranging from 6.7% to 100%. When tested over a range of temperatures from 15°C to 35°C, 25°C was found to be the optimal temperature for four selected nematode isolates (Steinernema carpocapsae All, Steinernema pakistanense 94-1, Heterorhabditis indica LN2 and H. indica 212-2) to infect the third instar and reproduce in the cadavers. S. pakistanense 94-1 and H. indica 212-2 showed markedly greater heat-tolerance compared to S. carpocapsae All and H. indica LN2. Corrected mortalities and reproduction rates increased as the concentration of IJs increased from 4 to 36 IJs cm−2. The LC50 values of S. carpocapsae All, S. pakistanense 94-1, H. indica LN2 and 212-2 were 17.1, 15.5, 6.5 and 5.9 IJs cm−2, respectively. The third instars larvae and pupae of P. striolata were more susceptible to the four nematode isolates than the first and second instars. Higher pathogenicity and greater heat tolerance and reproduction potential makes H. indica 212-2 the most promising candidate for the biological control of P. striolata under the field conditions of South China.

The mechanical properties of nanoporous Au (NPG) thin films were investigated by uniaxial microtensile tests. Such mechanical parameters as Young’s modulus, tensile strength, and breaking strain were obtained from the recorded force–displacement curves. Through observations on the microstructure and fracture surface morphology of the samples after the tension tests by a scanning electronic microscope (SEM) and an optical microscope, we analyzed the physical mechanisms underlying the mechanical behavior of NPG thin films. It was found that the NPG films exhibit mechanical properties distinctly different from its bulk counterpart.

This study reports a facile hydrothermal method for the synthesis of monodispersed hematite (α-Fe2O3) nanodiscs under mild conditions. The method has features such as no use of surfactants, no toxic precursors, and no requirements of high-temperature decomposition of iron precursors in non-polar solvents. By this method, α-Fe2O3 nanodiscs were achieved with diameter of 50 ± 10 nm and thickness of ~6.5 nm by the hydrolysis of ferric chloride. The particle characteristics (e.g., shape, size, and distribution) and functional properties (e.g., magnetic and catalytic properties) were investigated by various advanced techniques, including TEM, AFM, XRD, BET, and SQUID. Such nanodiscs were proved to show unique magnetic properties, i.e., superparamagnetic property at a low temperature (e.g., 20 K) but ferromagnetic property at a room temperature (~300 K). They also exhibit low-temperature (