Production and characterization of novel monoclonal antibodies against pathological human TDP-43 proteins.

The RNA/DNA-binding protein TDP-43 plays a pivotal role in the ubiquitinated inclusions characteristic of TDP-43 proteinopathies, including most cases of frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer disease (AD). To understand the mechanisms of pathological TDP-43 processing and identify potential biomarkers, we generated novel phosphorylation-independent monoclonal antibodies (MAbs) using bacteria-expressed human full-length recombinant TDP-43. Remarkably, we identified a distinctive MAb, No. 9, targeting an epitope in amino acid (aa) region 311-360 of the C-terminus. This antibody showed preferential reactivity for pathological TDP-43 inclusions, with only mild reactivity for normal nuclear TDP-43. MAb No. 9 revealed more pathology in FTLD-TDP type A and type B brains and in AD brains compared to the commercial p409/410 MAb. Using synthetic phosphorylated peptides, we also obtained MAbs targeting the p409/410 epitope. Interestingly, MAb No. 14 was found to reveal additional pathology in AD compared to the commercial p409/410 MAb, specifically, TDP-43-immunopositive deposits with amyloid plaques in AD brains. These unique immunopositivities observed with MAbs No. 9 and No. 14 are likely attributed to their conformation-dependent binding to TDP-43 inclusions. We expect that this novel set of MAbs will prove valuable as tools for future patient-oriented investigations into TDP-43 proteinopathies.

Cognitive behavioural therapy for depression, quality of life, and cognitive function in the post-stroke period: systematic review and meta-analysis.

The post-stroke period is associated with a lot of sequelae, including depression, decreased quality of life, and decline of cognitive function. Apart from the pharmacotherapy, it is also important to find a non-pharmacological treatment to relieve the sequelae. Cognitive behavioural therapy (CBT) might be a potential candidate, which can be clarified by a systematic review and meta-analysis. The eligible criteria of enrolled studies in the systematic review and meta-analysis were the randomised clinical trials (RCTs) using CBT to treat post-stroke depression, or with the focus on quality of life or cognitive function in the post-stroke period. The endpoint scores of depression, quality of life, and cognitive function scales were the targeted outcome for the final meta-analysis in the random effects model. Ten RCTs with 432 post-stroke patients receiving CBT and 385 controls were included. The meta-analysis results showed significant improvements in depression severity and quality of life. However, no significant difference between CBT and control groups was found in cognitive function. In addition, significant heterogeneity was derived from the meta-analysis. According to the meta-analysis results, CBT might be beneficial for relieving depression severity and improving quality of life. However, cognitive function might not be influenced by CBT. Further studies with a more consistent CBT design with greater sample sizes should be warranted to clarify and confirm the treatment effects of CBT for post-stroke depression and quality of life.

Layer-by-layer self-assembly embedding of nattokinase in chitosan/γ-polyglutamic acid: Preparation, fibrinolytic activity, stability, and in vitro digestion study.

Nattokinase (NK) is a thrombolytic enzyme extracted from natto, which can be used to prevent and treat blood clots. However, it is sensitive to the environment, especially the acidic environment of human stomach acid, and its effect of oral ingestion is minimal. This study aims to increase NK's oral and storage stability by embedding NK in microcapsules prepared with chitosan (CS) and γ-polyglutamic acid (γ-PGA). The paper prepared a double-layer NK oral delivery system by layer self-assembly and characterized its stability and in vitro simulated digestion. According to the research results, the bilayer putamen structure has a protective effect on NK, which not only maintains high activity in various environments (such as acid-base, high temperature) and long-term storage (60 days), but also effectively protects the loaded NK from being destroyed in gastric fluid and achieves its slow release. This work has proved the feasibility of the design of bilayer putamen structure in oral administration and has good fibrolytic activity. Therefore, the novel CS/γ-PGA microcapsules are expected to be used in nutraceutical delivery systems.

Integration of electronic nose, electronic tongue, and colorimeter in combination with chemometrics for monitoring the fermentation process of Tremella fuciformis.

This study proposes an efficient method for monitoring the submerged fermentation process of Tremella fuciformis (T. fuciformis) by integrating electronic nose (e-nose), electronic tongue (e-tongue), and colorimeter sensors using a data fusion strategy. Chemometrics was employed to establish qualitative identification and quantitative prediction models. The Pearson correlation analysis was applied to extract features from the e-nose and tongue sensor arrays. The optimal sensor arrays for monitoring the submerged fermentation process of T. fuciformis were obtained, and four different data fusion methods were developed by incorporating the colorimeter data features. To achieve qualitative identification, the physicochemical data and principal component analysis (PCA) results were utilized to determine three stages of the fermentation process. The fusion signal based on full features proved to be the optimal data fusion method, exhibiting the highest accuracy across different models. Notably, random forest (RF) was shown to be the most accurate pattern recognition method in this paper. For quantitative prediction, partial least squares regression (PLSR) and support vector regression (SVR) were employed to predict the sugar content and dry cell weight during fermentation. The best respective predictive R2 values for reducing sugar, tremella polysaccharide and dry cell weight were found to be 0.965, 0.988, and 0.970. Furthermore, due to its ability to capture nonlinear data relationships, SVR had superior performance in prediction modeling than PLSR. The results demonstrated that the combination of electronic sensor fusion signals and chemometrics provided a promising method for effectively monitoring T. fuciformis fermentation.

Therapeutic Effects of Dry Needling on Lateral Epicondylitis: An Updated Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the therapeutic effects of dry needling on lateral epicondylitis and identify a relatively more effective needling technique. DATA SOURCES: English databases (Pubmed, Web of Science, Scopus, EBSCO, ScienceDirect, Taylor & Francis, ProQuest, Cochrane, Ovid, and Embase) and Chinese databases (China National Knowledge Infrastructure, Wanfang, and VIP) were searched. STUDY SELECTION: This study included randomized controlled trials for comparing the effectiveness of dry needling with other treatment methods for lateral epicondylitis. The primary outcome measures were pain intensity and elbow disability, while the secondary outcome measures included grip strength and upper limb function. DATA EXTRACTION: Data extraction was performed by 2 researchers who used the Cochrane risk of bias analysis tool and the Physiotherapy Evidence Database checklist to assess the risk of bias and methodological quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the quality of evidence. DATA SYNTHESIS: A total of 17 studies that involved 979 subjects were included in this research. Dry needling exhibited a significant advantage in improving pain intensity among patients with lateral epicondylitis within 1 week after treatment (mean difference [MD]=-0.95, 95% confidence interval [CI], -1.88 to -0.02). Within 1 week and in the follow-ups that exceeded 1 week, dry needling also demonstrated better improvement in elbow disability (<1 week: standardized mean difference [SMD]=-1.37, 95% CI, -1.88 to -0.86; ≥1 week: SMD=-1.32, 95% CI, -2.23 to -0.4) and grip strength (<1 week: SMD=0.27, 95% CI, 0.01 to 0.53; ≥1 week: SMD=0.45, 95% CI, 0.02 to 0.88). Trigger point dry needling with local twitch response exhibited more significant improvement in pain intensity within 1 week (MD=-1.09, 95% CI, -1.75 to -0.44). CONCLUSIONS: Dry needling demonstrates good therapeutic effects on pain intensity (within 1 week), function, and grip strength among patients with lateral epicondylitis. Local twitch response is necessary in treatment that targets trigger points.

Polygonum cuspidatum polysaccharide: A review of its extraction and purification, structure analysis, and biological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

Identification, in silico selection, and mechanistic investigation of antioxidant peptides from corn gluten meal hydrolysate.

Seven novel antioxidant peptides (AWF, LWQ, WIY, YLW, LAYW, LPWG, and LYFY) exhibiting a superior activity compared to trolox were identified through in silico screening. Among these, the four peptides (WIY, YLW, LAYW, and LYFY) displayed notably enhanced performance, with ABTS activity 2.58-3.26 times and ORAC activity 5.19-8.63 times higher than trolox. Quantum chemical calculations revealed that the phenolic hydroxyl group in tyrosine and the nitrogen-hydrogen bond in the indole ring of tryptophan serve as the critical sites for antioxidant activity. These findings likely account for the potent chemical antioxidant activity. The corn peptides also exerted a protective effect against AAPH-induced cytomorphologic changes in human erythrocytes by modulating the antioxidant system. Notably, LAYW exhibited the most pronounced cytoprotective effects, potentially due to its high content of hydrophobic amino acids.

Influence of Nitrogen-Modified Atmosphere Storage on Lipid Oxidation of Peanuts: From a Lipidomic Perspective.

The effect of nitrogen-modified atmosphere storage (NS) on peanut lipid oxidation was investigated in this paper. Non-targeted lipidomics was employed to detect the lipid metabolites in peanuts with the aim of exploring the mechanism of lipid oxidation in peanuts under different storage conditions. The results showed that compared with conventional storage (CS), NS significantly (p < 0.05) delayed the increase in acid value, carbonyl value, and 2-thiobarbituric acid value and the decrease in vitamin E content. However, the storage time has a much greater effect on lipid oxidation than the oxygen level in the storage environment. Lipidomics analysis revealed that there were significant differences in metabolite changes between CS and NS. NS reduced the decline of most glycerophospholipids by regulating lipid metabolism in peanuts. NS maintained higher levels of Diacylglycerol (DAG), sulfoquinovosyl diacylglycerol (SQDG), lysophophatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and phosphatidylinositol (PI) compared to CS. This work provided a basis for the application of NS technology to peanut storage.

Total Synthesis of Ganoderma Meroterpenoids Cochlearol B and Its Congeners Driven by Structural Similarity and Biological Homology.

Secondary metabolites that have the same biological origin must share some relationship in their biosynthesis. Exploring this relationship has always been a significant task for synthetic biologists. However, from the perspective of synthetic chemists, it is equally important to propose, prove, or refute potential biosynthetic pathways in order to elucidate and understand the biosynthesis of homologous secondary metabolites. In this study, driven by the high structural similarity between the homologous Ganoderma meroterpenoids cochlearol B and ganocin B, two chemically synthetic strategies were designed and investigated sequentially for the synthesis of cochlearol B from ganocin B. These strategies include intramolecular metal-catalyzed hydrogen atom transfer (MHAT) and intramolecular photochemical [2+2] cycloaddition. The aim was to reveal their potential biosynthetic conversion relationship using chemical synthesis methods. As a result, a highly efficient total synthesis of cochlearol B, cochlearol T, cochlearol F, as well as the formal total synthesis of ganocins A-B, and ganocochlearins C-D, has been achieved. Additionally, a novel synthetic approach for the synthesis of 6,6-disubstituted 6H-dibenzo[b,d]pyran and its analogues has been developed through palladium(II)-catalyzed Wacker-type/cross-coupling cascade reactions.

Clinical Significance of Contrast-Enhanced Ultrasound Galactography in Pre-operative Diagnosis of Patients With Pathologic Nipple Discharge.

OBJECTIVE: The aim of the work described here was to investigate the feasibility and diagnostic value of using contrast-enhanced ultrasound (CEUS) galactography with SonoVue in patients with pathologic nipple discharge (PND). METHODS: Twenty-eight patients who underwent breast surgery for PND from May 2019 to August 2021 were included. Routine ultrasound, ductoscopy and CEUS galactography were performed successively. Lesions were diagnosed and localized. The sensitivity, specificity and pre-operative localization value of each examination method were evaluated on post-operative pathology. RESULTS: CEUS galactography was successfully conducted in all 28 patients and revealed negative ductal ectasia, filling stop and filling defect. Ductoscopy revealed positive nodules in 21 cases and negative nodules in 7 cases. A total of 18 nodules were found by routine ultrasound, and the relationship between all nodules and the discharge duct was confirmed after CEUS galactography. Compared with the other two methods, CEUS galactography had higher sensitivity, positive predictive value and negative predictive value (100%, 81.82% and 100%, respectively), while it has the same specificity as routine ultrasound (both 60%). The pre-operative location of the nipple duct was consistent with the intra-operative findings in 28 patients after CEUS galactography. CONCLUSION: The ultrasound contrast agent SonoVue can be used for CEUS galactography in patients with PND. CEUS galactography can improve the detection of ductal nodules and locate the nipple discharge duct pre-operatively. As the technique does not emit radiation and SonoVue is easily metabolized and safe, CEUS galactography is better than conventional imaging for PND patients.

Effects of ultrasonic-enzymatic-assisted ethanol precipitation method on the physicochemical characteristics, antioxidant and hypoglycemic activities of Tremella fuciformis polysaccharides.

This investigation involved the extraction of a novel polysaccharide from the spore fermentation broth of Tremella fuciformis using a method that combined ultrasonic and enzymatic assistance with ethanol precipitation. It was then compared with enzymatic and ultrasonic extraction methods. The objective of this research is to offer a reference point for expanding the application of ultrasonic-assisted enzymatic extraction technology in T. fuciformis polysaccharides (TFPs). Based on single-factor experiments, Box-Behnken was used to optimize the extraction conditions of TFPs by ultrasonic-enzymatic-assisted ethanol precipitation extraction. The results revealed an optimal combination of enzymes, with a cellulase-to-papain ratio of 2:1, an enzyme addition of 4000U/100 mL, an enzymolysis temperature of 49 °C, ultrasonicpower at 3 W/mL and an ultrasonictime of 20 min. The extraction rate of TFPs and α- amylase inhibition rates were 23.94 % and 61.44 %, respectively. Comparing the physicochemical properties, structural characterization and in vitro activity of TFPs extracted through different methods, the results showed that ultrasonic treatment significantly influences the apparent morphology of polysaccharide and could enhance its in vitro biological activity. However, different extraction techniques exhibit insubstantial impact on the chemical composition, glycosidic bonds or glycosidic ring configurations within the polysaccharides. Among them, ultrasonic-enzymatic-assisted ethanol precipitation extraction of polysaccharide has the highest extraction rate and the lowest viscosity. It has significant effects on ABTS+ scavenging activity, α- amylase inhibition rate and glucose dialysis retardation index, polysaccharide treated with ultrasonic-enzymatic showed the best performance. These findings suggest that ultrasonic-enzymatic-assisted ethanol precipitation extraction can enhance the activities of TFPs, thereby providing a valuable insight for their future development and application.

Lotus-Flower- and Lotus-Seedpod-Derived Polysaccharide: Structural Characterization and Biological Activity.

Lotus flower polysaccharide (LFP) and lotus seedpod polysaccharide (LSP) were separated by water extract-alcohol precipitation, and their structures and biological activities were investigated. The results of monosaccharide composition showed that LFP and LSP were composed of nine monosaccharides, fucose, rhamnose, arabinose, glucose, galactose, mannose, fructose, galacturonic acid, and glucuronic acid, with the molar percentages of 0.18: 0.43: 2.26: 45.22: 32.14: 4.28: 8.20: 6.28: 1.01 and 2.70: 1.02: 8.15: 45.63: 20.63: 1.44: 2.59: 16.45. LSP and LFP exhibited molecular weights of 9.37 × 104 Da and 1.24 × 106 Da, respectively. SEM showed that LFP and LSP have similar structures; XRD analysis showed that both polysaccharides had crystalline structure and amorphous structure. The results of ABTS+, DPPH, hydroxyl radical scavenging experiment, and a reducing power experiment showed that LFP and LSP had good antioxidant capacity. Cell viability findings showed that polysaccharide concentrations of lotus flower and lotus seedpod could enhance cellular proliferation ranging from 25 to 400 µg/mL without cytotoxicity. By inducing the production of crucial proteins in the TLR4/NF-κB pathway, LFP and LSP were able to induce autophagy in RAW264.7, according to the results of the RT-PCR and Western blotting assays.

Preparation, identification, and application of PEG/ZIF-8@ Dendrobium huoshanense polysaccharide as an adjuvant to enhance immune responses.

Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with polysaccharides are excellent drug-delivery carriers with high loading capacity and pH sensitivity. This study describes the one-step encapsulation of Dendrobium huoshanense polysaccharides (DHP) in ZIF-8. The resultant PEG6000/ZIF-8@DHP complex exhibited drug release properties in acidic microenvironments, possessed water solubility, demonstrated high drug loading capacity, and displayed effective encapsulation. The effects of PEG6000/ZIF-8@ DHP administration on immunoregulation, antioxidant activities, and resistance against Aeromonas veronii in channel catfish were assessed. The study revealed that the PEG6000/ZIF-8@DHP complex stimulated cellular proliferation and phagocytosis, while also inducing the production of cytokines and nitric oxide. Additionally, the complex exhibited improved antioxidant properties and increased serum lysozyme and alkaline phosphatase activities. PEG6000/ZIF-8@DHP exhibited efficacy in vivo against Aeromonas veronii infection. These results indicate that PEG6000/ZIF-8@DHP is an efficient immunostimulant and vaccine adjuvant for enhancing immunity in channel catfish.

High Formate Selectivity and Deactivation Mechanism of CuS Nanoparticles in CO2 Electrocatalytic Reduction Reaction.

CO2 electroreduction into liquid fuels is of broad interest and benefits reducing the energy crisis and environment burdens. CuS has been reported to be a desirable candidate for CO2 electroreduction into formate; however, its formate selectivity and stability are still far from the demands of practical application. Herein, we report CuS nanoparticles exhibiting good Faradaic efficiency of formate (about 98 %) in CO2 electroreduction and its deactivation mechanism during the reaction. The deactivation of CuS was found to be associated with the reconstruction and S loss of CuS, which deteriorates the Faradaic efficiency of formate. Combined with ionic and gas analyses, the S atom in CuS was lost in the form of H2 S, SO2 , and SO4 2- , followed by the reconstruction of CuS into copper oxides. Such a catalyst reconstruction facilitates electroreductions of CO2 and H2 O, respectively, into CO and H2 , etc., resulting in the degradation of catalytical performance of CO2 electroreduction into formate. This work reveals the important role of S loss and reconstruction of metal sulfide catalysts during the electroreduction reaction, which may benefit the further development of CuS-based electro-catalyst for CO2 electroreduction.

Corrigendum: Self-assembling and pH-Responsive protein nanoparticle as potential platform for targeted tumor therapy.

[This corrects the article DOI: 10.3389/fmolb.2023.1172100.].

Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy.

Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.

High interspecific competitiveness of the invasive plant Xanthium italicum Moretti severely reduces the yield and quality of Carthamus tinctorius L.

Safflower is an annual herb of Compositae, which has great economic value. To explore the impact of invasive weed Xanthium italicum Moretti on the economic crop safflower, field experiments were conducted, the growth-related characters and the relative intensity of competition between the two species was explored. The results showed that under monoculture conditions, the stem height, crown width, stem diameter and the biomass of X. italicum root, stem and leaves were 1.14, 1.96, 1.82, 4.42, 4.21 and 3.99 times as high as those of safflower, respectively. When the two species coexisted, the growth related characters of X. italicum were further significantly improved, while the growth related characters of safflower were significantly decreased. When coexisted with X. italicum, the corolla biomass, hydroxysafflor yellow A content of corolla, seed yields, 100-seed weight, and seed oil content of safflower in the interplanted treatment 90.04%, 33.11%, 63.89%, 40.58%, and 25.61% lower than those in the monocultured treatment, respectively. Relative yield (RY) and Competitive balance index (CB) of X. italicum and safflower showed that the interspecific competitiveness of X. italicum was significantly higher than that of safflower. Under the competitive inhibition of X. italicum, not only the vegetative growth, but also the reproductive growth, yield, and quality of the economic organs of safflower were significantly negatively impacted. Together, our findings provide important scientific basis for evaluating the invasion risks and consequences of safflower's cropland ecosystem by X. italicum.

The Potential Diagnostic Biomarkers for the IgG Subclass in Coal Workers' Pneumoconiosis.

Evidence suggests that exposure to coal dust increases immunoglobulin concentration. However, there is a paucity of data reporting immunoglobulin G (IgG) subclass in coal workers' pneumoconiosis (CWP). Therefore, this study intended to evaluate potential diagnostic biomarkers for the disease. CWP patients, dust-exposed workers without pneumoconiosis (DEW), and matched healthy controls (HCs) presented to the General Hospital of Datong Coal Mining Group and Occupational Disease Prevention and Treatment Hospital of Datong Coal Mining Group between May 2019 and September 2019 were recruited. The serum immunoglobulin concentration was determined by the multiplex immunoassay technique. Totally, 104 CWP patients, 109 DEWs, and 74 HCs were enrolled. Serum levels of IgG1, IgG2, IgM, and IgA were elevated in CWPs compared with those in DEWs and HCs (P < 0.05). The order of diagnostic accuracy between CWPs and DEWs depicted by the receiver operating characteristic (ROC) curve was IgG2, IgM, IgG1, IgG3, and IgA. Significantly higher IgG1/IgG3 and IgG2/IgG3 ratios were observed in the CWP group than in DEW and HC groups. Based on the IgG2/IgG3 ratio, the area under the ROC curve between CWP and DEW was 0.785 (95% CI 0.723-0.838), with a sensitivity of 73.1% and a specificity of 73.4%. Our findings suggest that IgG1, IgG2, IgM, and IgA are higher in the CWPs than DEWs and HCs. The IgG2/IgG3 ratio provides a viable alternative for the diagnosis of CWP.