Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Towards a new avenue for rapid synthesis of electrocatalytic electrodes via laser-induced hydrothermal reaction for water splitting

Electrochemical production of hydrogen from water requires the development ofelectrocatalysts that are active,stable,and low-cost for water splitting.To address these challenges,researchers are increasingly exploring binder-free electrocatalytic integratedelectrodes (IEs) as an alternative to conventional powder-based electrode preparation methods,for the former is highly desirable to improve the catalytic activity and long-term stability for large-scale applications of electrocatalysts.Herein,we demonstrate a laser-inducedhydrothermal reaction (LIHR) technique to grow NiMoO4nanosheets on nickel foam,which is then calcined under H2/Ar mixed gases to prepare the IE IE-NiMo-LR.This electrode exhibits superior hydrogen evolution reaction performance,requiring overpotentials of 59,116 and143 mV to achieve current densities of 100,500 and 1000 mA·cm-2.During the 350 h chronopotentiometry test at current densities of 100 and 500 m A·cm-2,the overpotentialremains essentially unchanged.In addition,NiFe-layered double hydroxide grown on Ni foam is also fabricated with the same LIHR method and coupled with IE-NiMo-IR to achieve water splitting.This combination exhibits excellent durability under industrial current density.The energy consumption and production efficiency of the LIHR method are systematicallycompared with the conventional hydrothermal method.The LIHR method significantly improves the production rate by over 19 times,while consuming only 27.78%of the total energy required by conventional hydrothermal methods to achieve the same production.

Cardiac infiltration of diffuse large B-cell lymphoma manifesting as sustained ventricular tachycardia:a case report

Cardiac tumors are rare.However,cardiac metastases can occur in up to 10%of patients with cancer.Among cardiac neoplasms,metastases are much more common than primary cardiac tumors.[1]Metastatic cardiac neoplasms most frequently metastasize from the respiratory system.

Separation of Pd and Pt from highly acidic leach liquor of spent automobile catalysts with monothio-Cyanex 272 and trioctylamine

Platinum group metals(PGMs),especially Pd,Pt,and Rh,have drawn great attention due to their unique features.Direct separation of Pd and Pt from highly acidic automobile catalyst leach liquors is disturbed by various factors.This work investigates the effect of various parameters including the acidity,extractant concentration,phase ratio A/O,and diluents on the Pd and Pt extraction and their stripping behaviors.The results show that the Pd and Pt are successfully separated from simulated leach liquor of spent automobile catalysts with monothioCyanex 272 and trioctylamine(TOA).Monothio-Cyanex 272 shows strong extractability and specific selectivity for Pd,and only one single stage is needed to recover more than 99.9% of Pd,leaving behind all the Pt,Rh,and base metals of Fe,Mg,Ce,Ni,Cu,and Co in the raffinate.The loaded Pd is efficiently stripped by acidic thiourea solutions.TOA shows strong extractability for Pt and Fe at acidity of 6 mol·L^(–1) HCl.More than 99.9% of Pt and all of the Fe are extracted into the organic phase after two stages of countercurrent extraction.Diluted HCl easily scrubs the loaded base metals(Fe,Cu,and Co).The loaded Pt is efficiently stripped by 1.0 mol·L^(–1) thiourea and 0.05–0.1 mol·L^(–1) Na OH solutions.Monothio-Cyanex 272 and TOA can realize the separation of Pd and Pt from highly acidic leach liquor of spent automobile catalysts.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

优化合成工艺的增韧预浸料树脂及其复合材料的性能

根据流变性能、凝胶时间等参数确定了预浸料树脂的基础配方,并根据固化后树脂浇注体表面质量优化预浸料树脂的合成工艺,降低能耗的同时解决了双氰胺分散不均的问题。引入气相纳米SiO_(2)组分作为增韧剂(最佳添加量为1%),增韧后树脂浇注体拉伸强度为74.41 MPa、冲击强度为20.23 kJ/m^(2),比原配方分别提高了72.64%和58.79%。最终确定预浸料树脂配方为E-51、E-20、NPCN704、双氰胺、二氯苯基二甲脲、气相纳米SiO_(2)和消泡剂的质量比50:30:20:7:2:1:0.2,根据差示扫描量热分析(DSC)的非等温曲线外推法确定树脂配方的固化工艺为100℃/1 h+130℃/2 h+150℃/2 h。将自制预浸料树脂与商用预浸料树脂进行浇注体和复合材料的力学性能对比,结果表明,自制预浸料树脂各项性能较为优异。采用真空辅助成型工艺制备了玻纤和碳纤增强自制预浸料树脂复合材料,树脂含量分别控制在40%和35%为宜。

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

AIM:To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acuteon-chronic liver failure(HBV-ACLF).METHODS:Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed.Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS:A total of 190 patients were included in this study.The overall 1-year survival rate was 57.6%.Patients not treated with antiviral drugs had a significantly higher mortality[relative risk(RR)=0.609,P=0.014].The highest risk of death in patients with ACLF was associated with hepatorenal syndrome(HRS)(RR=2.084,P=0.026),while other significant factors were electrolyte disturbances(RR=2.062,P=0.010),and hepatic encephalopathy(HE)(RR=1.879,P<0.001).CONCLUSION:Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate.HRS,electrolyte disturbances,and HE also affect patient survival.

Role of macrophages in peripheral nerve injury and repair

Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory (Ml) and anti-inflammatory (M2) actions, and M2 macrophages have four subtypes. The co-action of Ml and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.

Three-liquid-phase extraction and separation of V(V) and Cr(VI) from acidic leach solutions of high-chromium vanadium–titanium magnetite

A new method by liquid–liquid–liquid three phase system, consisting of acidified primary amine N1923(abbreviated as A-N1923), poly(ethylene glycol)(PEG) and (NH_4)_2SO_4 aqueous solution, was suggested for the separation and simultaneous extraction of V(V) and Cr(VI) from the acidic leach solutions of highchromium vanadium–titanium magnetite. Experimental results indicated that V(V) and Cr(VI) could be selectively enriched into the A-N1923 organic top phase and PEG-rich middle phase, respectively, while Al(III)and other co-existing impurity ions, such as Si(IV), Fe(III), Ti(IV), Mg(II) and Ca(II) in acidic leach solutions,could be enriched in the(NH_4)_2SO_4 bottom aqueous phase. During the process for extraction and separation of V(V) and Cr(VI), almost all of impurity ions could be removed. The separation factors between V(V) and Cr(VI) could reach 630 and 908, respectively in the organic top phase and PEG middle phase, and yields of recovered V(V) and Cr(VI) in the top phase and middle phase respectively were all above 90%.Various effects including aqueous p H, A-N1923 concentration, PEG added amount and(NH_4)_2SO_4 concentration on three-phase partitioning of V(V) and Cr(VI) were discussed. It was found that the partition of Cr(VI) into the PEG-rich middle phase was driven by hydrophobic interaction, while extraction of V(V) by A-N1923 resulted of anion exchange between NO_3^- and H_2V_(10)O_(28)^(-4). Stripping of V(V) and Cr(VI) from the top organic phase and the middle PEG-rich phase were achieved by mixing respectively with NaNO_3 aqueous solutions and Na OH-((NH_4)_2SO_4 solutions. The present work highlights a new approach for the extraction and purification of V and Cr from the complex multi-metal co-existing acidic leach solutions of high-chromium vanadium–titanium magnetite.

Rational Design of Hybrid Peptides: A Novel Drug Design Approach

Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural peptides are not always ideal choices for clinical application due to their limited number and sometimes cytotoxicity to normal cells. Aiming to gain stronger or specific or novel biological effects and overcome the disadvantages of natural peptides, artificial hybrid peptides have been designed by combining the sequence of two or more different peptides with varied biological functions. Compared to natural peptides, hybrid peptides have shown better therapeutic potentials against bacteria, tumors, and metabolic diseases. In this review, design strategies, structure features and recent development of hybrid peptides are summarized;future directions for the research and development of hybrid peptide drugs are also discussed.

A Fast and Memory-Efficient Approach to NDN Name Lookup

For name-based routing/switching in NDN, the key challenges are to manage large-scale forwarding Tables, to lookup long names of variable lengths, and to deal with frequent updates. Hashing associated with proper length-detecting is a straightforward yet efficient solution. Binary search strategy can reduce the number of required hash detecting in the worst case. However, to assure the searching path correct in such a schema, either backtrack searching or redundantly storing some prefixes is required, leading to performance or memory issues as a result. In this paper, we make a deep study on the binary search, and propose a novel mechanism to ensure correct searching path without neither additional backtrack costs nor redundant memory consumptions. Along any binary search path, a bloom filter is employed at each branching point to verify whether a said prefix is present, instead of storing that prefix here. By this means, we can gain significantly optimization on memory efficiency, at the cost of bloom checking before each detecting. Our evaluation experiments on both real-world and randomly synthesized data sets demonstrate our superiorities

Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

Grouping separation of mixed rare earths from their coexisting aqueous solutions by liquid-column elution

A new approach was proposed for grouping separation of 14 lanthanide rare-earth ions from their coexisting mixed aqueous solutions, by performing liquid-column elution using the aqueous solution containing 14 lanthanide rare-earth ions as the stationary phase and the dispersed organic oil droplets containing P507 extractant as the mobile phase. It was revealed that 14 lanthanide rare-earth ions could be separated into four groups, according to the lanthanide tetrad effect, respectively eluting out from the liquid column at different time in a certain order. Various effects including the saponification degree of P507, the concentration of P507 in organic phase, the length and inner diameter of the extraction column on the performance of grouping separation of rare-earth ions were discussed. The changes of the mass transfer coefficients were also investigated. The separation efficiency of the four groups of rareearth elements(REEs) was evaluated based on the elution resolution, Rs, of the elution peaks of La(Ⅲ),Gd(Ⅲ), Ho(Ⅲ) and Lu(Ⅲ), the four representative elements respectively from each of the four groups of REEs. Experimental results demonstrated that the separation of REEs by liquid-column elution mainly depended on the competitive adsorption of different rare-earth groups onto the surface of ascending P507 oil droplets. The affinity of different rare-earth groups with P507 extractant and a limited adsorption capacity of P507 molecules at the surface of the oil droplets ascending in liquid column play the important role. The present work highlights a promising technique for grouping separation of multiple lanthanide elements co-existing complex systems.

Effect of Combined Application of Organic Fertilizer and Chemical Fertilizer in Different Ratios on Growth,Yield and Quality of Fluecured Tobacco

The effect of different ratio of organic and inorganic fertilizers on the growth and the yield and quality of flue-cured tobacco was studied.Using randomized blocks design,the data of the test materials K326 were analyzed by using variance analysis,significance test and other methods.The release efficiency of organic fertilizer in the soil was slower,and the effect of organic fertilizer on the growth of tobacco plants was worse than that of chemical fertilizers,and under 25% organic fertilizer + 75% chemical fertilizer treatment,the quality of the fluecured tobacco was good.Under the treatment of 50% organic fertilizer + 50% chemical fertilizer,the production of flue-cured tobacco was high and the ratio of first-class tobacco was high.It is suggested that the organic fertilizer application ratio should be 25%-50% in the agricultural production.

Risk factors related to postoperative recurrence of dermatofibrosarcoma protuberans: A retrospective study and literature review

BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare low-grade malignant soft tissue tumor characterized by rosette-like infiltrative growth.Postoperative recurrence of this tumor is very common.AIM To evaluate the risk factors related to recurrence after wide local excision(WLE)of DFSP and to guide clinical diagnosis and treatment.METHODS The medical records of 44 DFSP patients confirmed by pathology at our hospital from 2012 to 2019 were retrospectively reviewed.The relationship between clinical features,tumor characteristics,treatment,and recurrence risk were analyzed,and the possible risk factors for postoperative tumor recurrence were evaluated.RESULTS There were 44 patients in total,including 21 males and 23 females.The median progression free survival was 36 mo(range,1-240 mo).Twenty patients were treated for the first time,while 24 had previous treatment experience.Forty-two cases were followed for 25.76±22.0 mo,among whom four(9.52%)experienced recurrence after WLE(rate was 9.52%).The recurrence rate in the recurrent group was higher than that in the patients with primary tumor(19.05%vs 0%,P=0.028).Eighteen cases had a history of misdiagnosis(rate was 40.91%).The recurrence rate among patients with previous experience of misdiagnosis was significantly higher than in patients without(68%vs 36.84%,P=0.04).The tumor diameter in patients with a history of treatment was larger than in patients treated for the first time(4.75±0.70 cm vs 2.25±0.36 cm,P=0.004).CONCLUSION To sum up,the clinical manifestations of DFSP are not specific and are easily misdiagnosed,thus commonly causing the recurrence of DFSP.After incomplete resection,the tumor may rapidly grow.Previous recurrence history may be a risk factor for postoperative recurrence,and tumor location may have an indirect effect on postoperative recurrence;however,we found no significant correlation between sex,age,course of the disease,or tumor size and postoperative recurrence.

A novel constant interfacial area cell for determining the extraction kinetics of Er(Ⅲ) from chloride medium

A novel constant interfacial area cell(NCIAC),by spatially separating the agitation from liquid flow circulation of organic and aqueous two phases,was suggested to obtain detailed kinetic data for Er(Ⅲ) extraction from chloride medium by 2-ethyl-hexyl-phosphonic acid mono-(2-ethylhexyl) ester(EHEHPA).Different from the traditional Lewis cell and the constant interfacial area cell with laminar flow,the concentrations of Er(Ⅲ) in organic and aqueous two phases were uniform,and the stability of the interfacial area between the two phases could be controlled effectively.Therefore,the special requirements for the design of agitators in the traditional Lewis cell and the constant interfacial area cell for minimizing the influence of diffusion resistance could be avoided.Experimental results indicated that the extraction kinetics was mainly affected by the aqueous flow rate,interfacial area between organic and aqueous two phases,and the aqueous p H values.An extraction kinetic equation was suggested based on the experimental data.

Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model

AIM:To investigate the possible role of chitinase3-like-1(CHI3L1)in the progression of colitis-associated carcinoma(CAC).METHODS:Thirty-four Balb/c mice were randomly assigned to five groups,including the control,CAC control,CAC+caffeine,colitis control and colitis+caffeine.Three animals were sacrificed every two weeks for blinded macroscopic inspection,histological analysis,and total RNA extraction.An immunofluorescent assay was performed using specimens from the colitis control and colitis+caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage.In vitro,HT29 cells prestimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFHDA fluorescent probe to determine the effect of CHI3L1on intracellular reactive oxygen species production.RESULTS:CHI3L1 mRNA was increased during the progression of colon carcinogenesis.Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon.Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice.CHI3L1protein increased reactive oxygen species in HT29 cells when exposed to H2O2.CONCLUSION:Caffeine reduces tumor incidence by decreasing oxidative DNA damage.CHI3L1 may contribute to CAC by increasing reactive oxygen species production.

Long-term cross-border electricity trading model under the background of Global Energy Interconnection

Environmental problems caused by traditional power production and the unbalanced distribution of energy resources and demand limit the development of sustainable societies. A feasible method to optimize the resource allocation has been proposed, and it involves cross-border and cross-regional electricity transactions. However, the uncertainty of renewable energy and the specific features of the cross-border electricity market are key issues which need to be considered in the trading mechanism design. Based on this, this paper sets up a long-term cross-border electricity trading model considering the uncertainty of renewable energy. First, annual transactions are matched according to the declared data of bidders with consideration of cross-border interconnection development benefits, potential benefit risks, and transmission costs. Second, for annual contract decomposition, the model uses the minimum generation cost function with a penalty item for power shortages to allocate electricity to each month. Additionally, the scenario reduction algorithm is combined with the unit commitment to construct a stochastic generation plan. Finally, a case study of the numerical results for the multinational electricity market in northeast Asia is used to show that the proposed trading model is feasible for cross-border electricity trading with high penetration of renewable energy.

Inhibition of PARP1 Increases IRF-dependent Gene Transcription in Jurkat Cells

Poly(ADP-ribose) polymerase 1 (PARP1) plays important roles in the regulation of transcription factors. Mounting evidence has shown that inhibition of PARP1 influences the expression of genes associated with inflammatory response. Interferon regulatory factor 1 (IRF1) is a critical transcription factor for the development of both the innate and adaptive immune responses against infections. However, the molecular mechanism through which PARP1 mediates the effects has not been clearly demonstrated. Jurkat cells were exposed to dexamethasone (Dex) or PARP1 inhibitor PJ34. The expression levels of IL-12, LMP2, OAS1 and PKR were detected using real-time RT-PCR. The interactions between PARP1 and IRF1 were examined by coimmunoprecipitation (co-IP) assays. We further explored the mechanism of PARP1 suppressing IRF1 by assessing the activities of interferon stimulated response element (ISRE). The mRNA expression of IL-12, LMP2, OAS1 and PKR was obviously suppressed by Dex in Jurkat cells, which could be rescued by PJ34 treatment. Luciferase study revealed that poly(ADP-ribosyl)- ation suppressed IRF1-mediated transcription through preventing the binding of IRF1 to ISREs. PARP1 inhibited IRF1-mediated transcription in Jurkat cells by preventing IRF1 binding to ISREs in the promoters of target genes. It is suggested that PARP1 is a crucial regulator of IRF1-mediated immune response. This study provides experimental evidence for the possible application of PARP1 inhibitors in the treatment of IRF1-related immune anergy.

Relationship between Atrial Tissue Remodeling and ECG Features in Atrial Fibrillation

The difference in the atrial organizational structure between patients with atrial fibrillation (AF) and those with sinus rhythm was investigated.In order to analyze the rationality in explaining the electrocardiogram (ECG) characteristics of AF with statistics data or tissue remodeling model,and the logical relationship between the hypothesis of pulmonary veins (PV) muscle sleeves and that of multi wavelets in mechanism of AF,we examined the expression of collagen volume fraction of type I (CVF-I ) with picrosirius red staining,connexin 40 (Cx40) by immunohistochemistry,and intercalated disc (ID) using transmission electron microscope in atrial tissue.The results showed that there was significant difference in the expression of CVF-I (t=3.827,P<0.01),Cx40 (t=4.21,P<0.01),and groups of the ID that keeping the electrical transmission and atrial electrical coupling synchronization (t=15.116,P<0.001),but no significant difference was found in total IDs (t=0.611,P=0.543) between patients with AF and those with sinus rhythm.The quantitative differences in the tissue remodeling could not explain the ECG characteristics of AF.The number of normal IDs and abnormal distribution are the structural basis to trigger and maintain atrial electrical remodeling,and induce and maintain AF.Such histological reconstruction supports the hypothesis of multi wavelets and can also explain ECG features.