Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in ...EBVaGC is not yet fully understood.
We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively.
In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups.
Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.
This article presents a novel adaptive iterative learning control (AILC), and designs a human-in-loop control pattern (HIL-CP), which simulates the proposed approach using different lower limb ...rehabilitation robot models. The stability of the AILC controller is proposed and verified via a Lyapunov-like function, where novel controller shows strong robustness in disturbances environment. Based on AILC, the core of the HIL-CP interactive control mode is to estimate the human surface electromyography by neural network model and get the real-time desired trajectory to iterate out the optimal actual tracking trajectory, which reduce the tracking error quickly and ensure the rehabilitation training effect of patients. Furthermore, the MATLAB software is employed to conduct simulation experiments the proposed approach. The simulation results show that the HIL-CP is highly efficient and rapidly convergent in a satisfied degree. The angle error is
0.25
o
±
0.2
o
for patients and
0.03
o
±
0.02
o
for healthy people. Compared with the existing sliding mode controller, it is proven that the AILC controller is much more effective and noise-tolerant ability in the presence of bounded nonlinear disturbance.
A high-efficiency form-finding algorithm is crucially important for finding a stabilized tensegrity structure. In this paper, a modified Broyden-Fletcher-Goldfarb-Shanno noise-tolerant zeroing neural ...network (MBFGS-NTZNN) form-finding approach is developed and investigated for the form-finding problems of tensegrity systems. A modified BFGS algorithm (MBFGS) is employed to solve the irreversibility of the Hessian matrix, which could avoid the non-positive definite circumstance of the stiffness matrix. Additionally, the approach could be utilized to make a reduction in algorithm calculation complexity. Moreover, to find a group of suitable nodal coordinates, a zeroing neural network (ZNN) based NTZNN is considered to suppress the noise, which may include rounding errors and external disturbance during the form-finding process. Besides, the 0-stable and global convergence under the pollution of noise are verified. Eventually, numerical simulations and an application example are conducted to ascertain the superiority and availability of the MBFGS-NTZNN algorithm in the fields of form-finding.
The geographic variation in life-history traits of organisms and the mechanisms underlying adaptation are interesting ideas in evolutionary biology. This study investigated age and body size of the ...Asian common toad (Duttaphrynus melanostictus) among five populations along a geographical gradient. We found that geographical variation in age was non-significant among populations but there was a significant and positive correlation between mean age and body size. Although the body size values at 1043 m are quite different from other sites, after controlling for age effects, there was a significant positive correlation between altitude and body size. Our findings followed the predictions of Bergmann’s rule, suggesting that the body size of D. melanostictus is potentially influenced by the low air temperatures at higher altitudes.
With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the ...adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.
A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation
. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2'-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the
effect of MIR22HG on the radiosensitivity of hepatoma.
Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity
miR-22-5p in HCC.
Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.
Methadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), ...executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear.
Thirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined.
After 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score.
Long-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.
In order to extend the duration of the electrolyte solution in which copper granules recovered from waste printed circuit board are refined through electrolysis to obtain copper foil with high purity ...and which is contaminated by the accumulation of metallic impurities along with the refinery of waste printed circuit board, the leaching and electrowinning processes are used to pretreat the copper granules. The effects of impurities of copper granules as well as H
2
SO
4
mole ratio, leaching temperature, liquid-solid ratio, and operation time on the removing efficiencies of Zn, Sn, Fe and Al, were studied. The results showed that more than 95% of impurities can be removed when the mole ratio of impurities to H
2
SO
4
was 1:4, the temperature was 70 °C, the liquid-solid ratio was 20 mL/g, along with the leaching time of 180 min. After 1440 min electrolysis of the pretreated granules with the electric current density of 40 mA/cm
2
, the purity of refined copper foil maintained at 99% in contrast with 95% which copper granules are without pretreatment. The maximal concentration of the accumulated ions of impurities is less than 60 mg/L, which suggests that sulfuric acidic pretreatment is a promising approach to increase the duration of the electrolyte solution.
Graphical Abstract
Traumatic brain injury (TBI), recognized as the world's most serious public health problem, currently lacks effective treatment options. The development of the patch has great clinical significance ...whether it is used as a skull implant material or TBI repair. In response to this critical health challenge, a novel 3D‐printed bi‐layer cranial‐brain patch (SMB6) with dual functionality, addressing both TBI repair and skull regeneration, is developed. In the first layer, the incorporation of high concentrations of mesoporous bioactive glass nanoparticles establishes a microenvironment for bone regeneration. Meanwhile, the second layer, comprised of methacrylated silk fibroin hydrogel, provides essential mechanical support for nanocell membrane vesicles loaded with macrophage colony‐stimulating factor and interleukin‐6. This innovative design aims to interrupt the cascade of secondary brain injury. In experimental models of TBI, SMB6 demonstrates remarkable efficacy in inhibiting brain edema, exerting therapeutic effects on blood vessels, nerves, and inflammation. Additionally, promising outcomes are observed in promoting bone regeneration in skull defect models. This work not only introduces a potential therapeutic patch for TBI‐related diseases but also provides novel insights for the clinical translation of cranial patches.
Schematic showing a novel 3D‐printed bi‐layer cranial‐brain patch promotes traumatic brain injury repair and bone tissue regeneration. In the first layer, the incorporation of high concentrations of mesoporous bioactive glass establishes a microenvironment for bone regeneration. Meanwhile, the second layer is loaded with bio microglia that encapsulate macrophage colony‐stimulating factor and interleukin‐6 to block the secondary injury cascade.
The use of transition metal phosphides for hydrogen evolution reaction has been continuously reported in recent years, but their excessive H* adsorption is detrimental to H2 desorption, as well as ...their limited specific surface area restricts the exposure of their active sites. Herein, we synthesized CoP by a molten salt method and gas phosphorylation and obtained the target catalyst B-CoP by further treating it with NaBH4 solution. Under the action of NaBH4, a large number of oxide impurities on the surface of the catalyst precursor reacted, generating a large number of oxygen vacancies and partially transforming the CoP of the crystalline-phase structure into an amorphous phase, which resulted in a large number of pore structures and a substantial increase in the specific surface area of the generated B-CoP catalyst. The special nanostructure allows the catalyst to increase the contact area with the electrolyte and accelerates the desorption of gas bubbles, which results in the catalyst exhibiting such a superior catalytic activity, with overpotentials of 104, 156, and 188 mV at 100, 500, and 1000 mA cm−2 current densities, respectively, and can be operated stably at 100 mA cm−2 current density for 100 hours. This work provides new ideas for efficient catalysts for hydrogen evolution reaction from phosphides.
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•Partial transformation of CoP into an amorphous structure after NaBH4 treatment.•The specific surface area increases dramatically, exposing more active sites.•The partially amorphous CoP and the pore structure facilitate the desorption of H2.•B-CoP exhibits superior catalytic activity and stability over reported CoP catalysts.
The heat shock response (HSR) is a cellular protective mechanism that is characterized by the induction of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) in response to ...diverse cellular and environmental stressors, including cadmium (Cd). However, little is known about the relationship between the damaging effects of Cd and the HSR pathway in the chicken cerebrum following Cd exposure. To explore whether Cd exposure elicits cerebral damage and triggers the HSR pathway, chicks were exposed to Cd in the daily diet at different concentrations (35, 70, or 140 mg/kg feed) for 90 days, while a control group was fed the standard diet without Cd. Histopathological examination of cerebral tissue from Cd-exposed chickens showed neuronal damage, as evidenced by swelling and degeneration of neurons, loss of neurons, and capillary damage. Cd exposure significantly increased mRNA expression of HSF1, HSF2, and HSF3, and mRNA and protein expression of three major stress-inducible HSPs (HSP60, HSP70, and HSP90). Moreover, Cd exposure differentially modulated mRNA expression of small HSP (sHSPs), most notably reducing expression of HSP27 (HSPB1). Furthermore, Cd exposure increased TUNEL-positive neuronal apoptotic cells and up-regulated protein expression of caspase-1, caspase-8, caspase-3, and p53, leading to apoptosis. Taken together, these data demonstrate that activation of the HSR and apoptotic pathways by Cd exposure is involved in Cd-elicited cerebral damage in the chicken.
Graphical Abstract
Synopsis for the graphical abstract
Cadmium (Cd)-induced neuronal damage triggers the heat shock response (HSR) by activating heat shock transcription factors (HSFs) and subsequent induction of major heat shock proteins (notably, HSP60, HSP70, and HSP90). Moreover, Cd exposure activates caspase-1, caspase-8, caspase-3, and p53 protein, thereby resulting in neuronal apoptosis in the chicken brain.
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