Effect of roasted purple laver (nori) on vitamin B12 nutritional status of vegetarians: a dose-response trial.

PURPOSE: To investigate the bioavailability of vitamin B12 from nori and to evaluate the required dosage for improving vitamin B12 nutritional status in vegetarians not using supplements. METHODS: The study design is an open-label, parallel, dose-response randomized controlled trial. Thirty vegetarians were assigned to control (no nori), low-dose (5 g nori, aiming to provide 2.4 µg vitamin B12 per day), or high-dose (8 g nori, aiming to provide 4 µg vitamin B12 per day) groups. The primary outcome was changes in vitamin B12 status as measured by serum vitamin B12, holotranscobalamin (holoTC), homocysteine (Hcy), and methylmalonic acid (MMA), and a combined score of these four markers (4cB12 score) during the four-week intervention. Dietary vitamin B12 intakes were assessed at baseline and end of the trial with a 17-item food frequency questionnaire designed for vitamin B12 assessment. General linear model was used to compare least square means of changes in each biomarker of vitamin B12 status, among the three groups, while adjusting for respective baseline biomarker. RESULTS: After adjusting for baseline status, nori consumption led to significant improvement in serum vitamin B12 (among-group P-value = 0.0029), holoTC (P = 0.0127), Hcy (P = 0.0225), and 4cB12 (P = 0.0094). Changes in MMA did not differ significantly across groups, but showed within-group pre-post improvement in the low-dose group (median [p25, p75] = -339 [-461, -198] nmol/L). Vitamin B12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B12 (lease square mean [95% CI] = + 59 [25, 93] pmol/L, P = 0.0014); holoTC (+ 28.2 [10.1, 46.3] pmol/L, P = 0.0035); Hcy (-3.7 [-6.8, -0.6] µmol/L, p = 0.0226); and 4cB12 score (+ 0.67 [0.24, 1.09], p = 0.0036). High-dose resulted in similar improvements. There was no significant difference between low-dose and high-dose groups in all biomarkers of vitamin B12. CONCLUSIONS: Consuming 5 g of nori per day for 4 weeks significantly improved vitamin B12 status in vegetarians. A higher dose (8 g) may not confer additional benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05614960. Date of registration: November 14th 2022.

Terahertz-driven positron acceleration assisted by ultra-intense lasers.

Generation and acceleration of energetic positrons based on laser plasma have attracted intense attention due to their potential applications in medical physics, high energy physics, astrophysics and nuclear physics. However, such compact positron sources face a series of challenges including the beam dispersion, dephasing and unstability. Here, we propose a scheme that couples the all-optical generation of electron-positron pairs and rapid acceleration of copious positrons in the terahertz (THz) field. In the scheme, nanocoulomb-scale electrons are first captured in the wakefield and accelerated to 2.5 GeV. Then these energetic electrons emit strong THz radiation when they go through an aluminum foil. Subsequently, abundant γ photons and positrons are generated during the collision of GeV electron beam and the scattering laser. Due to the strong longitudinal acceleration field and the transvers confining field of the emitted THz wave, the positrons can be efficiently accelerated to 800 MeV, with the peak beam brilliance of 2.26 × 1012s-1mm-2mrad-2eV-1. This can arouse potential research interests from PW-class laser facilities together with a GeV electron beamline.

Asymmetric Synthesis of Axially Chiral Molecules via Organocatalytic Cycloaddition and Cyclization Reactions.

Atropisomeric molecules are present in many natural products, biologically active compounds, chiral ligands and catalysts. Many elegant methodologies have been developed to access axially chiral molecules. Among them, organocatalytic cycloaddition and cyclization have attracted much attention because they have been widely used in the asymmetric synthesis of biaryl/heterobiaryls atropisomers via construction of carbo- and hetero-cycles. This strategy has undoubtedly become and will continue to be a hot topic in the field of asymmetric synthesis and catalysis. This review aims to highlight the recent advancements in this field of atropisomer synthesis by using different organocatalysts in cycloaddition and cyclization strategies. The construction of each atropisomer, its possible mechanism, the role of catalysts, and its potential applications are illustrated.

Ultra-brilliant GeV betatronlike radiation from energetic electrons oscillating in frequency-downshifted laser pulses.

Electrons can be accelerated to GeV energies with high collimation via laser wakefield acceleration in the bubble regime and emit bright betatron radiation in a table-top size. However, the radiation brightness is usually limited to the third-generation synchrotron radiation facilities operating at similar photon energies. Using a two-stage plasma configuration, we propose a novel scheme for generating betatronlike radiation with an extremely high brilliance. In this scheme, the relativistic electrons inside the bubble injected from the first stage can catch up with the frequency-downshifted laser pulse formed in the second stage. The laser red shift originates from the phase modulation, together with the group velocity dispersion, which enables more energy to be transfered from the laser pulse to γ-photons, giving rise to ultra-brilliant betatronlike radiation. Multi-dimensional particle-in-cell simulations indicate that the radiated γ-photons have the cut-off energy of GeV and a peak brilliance of 1026 photons s-1 mm-2 mrad-2 per 0.1%BW at 1 MeV, which may have diverse applications in various fields.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Photodriven seawater splitting is considered to be one of the most promising techniques for sustainable hydrogen production. However, the high salinity of seawater would deactivate catalysts and consume the photogenerated carriers. Metal vacancies in metal oxide semiconductors are critical to directed electron transfer and high salinity resistance; they are thus desirable but remain a challenge. We demonstrate a facile controllable calcination approach to synthesize TiO2 nanofibers with rich Ti vacancies with excellent photo/electro performances and long-time stability in photodriven seawater splitting, including photocatalysis and photo-electrocatalysis. Experimental measurements and theoretical calculations reveal the formation of titanium vacancies, as well as unidirectional electron trap and superior H+ adsorption ability for efficient charge transfer and resistance to corrosion by seawater. Therefore, atomic-/nanoscale characteristics and mechanism have been proposed to clarify the generation of titanium vacancies and the corresponding interfacial electron transfer.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Invited for the cover of this issue are Xiao-Yu Yang and co-workers at Wuhan University of Technology, Heinrich-Heine-Universität Düsseldorf, University of the Witwatersrand, and Ben-Gurion University of the Negev. The image depicts Ti vacancies in TiO2 as powerful drivers of photo- and photo-electrocatalytic seawater splitting for hydrogen production. Read the full text of the article at 10.1002/chem.202101817.

ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt/ß-catenin signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells (LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase (ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown. METHODS: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/ß-catenin signaling by ACLY. Rescue experiments were performed to investigate whether ß-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells. RESULTS: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of ß-catenin, and Lys49 acetylation of ß-catenin might mediate ACLY-regulated ß-catenin level in HCC cells. CONCLUSIONS: ACLY is a potent regulator of Wnt/ß-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.

The evolutionary and transmission characteristic of HIV-1 CRF07_BC in Nanjing, Jiangsu.

To understand the epidemiology, evolutionary and transmission characteristics of HIV-1 CRF07_BC in Nanjing, China. One hundred and fifty-nine patients with HIV-1 CRF07_BC were recruited. DNA sequencing, phylogenetic analysis, and molecular transmission cluster analysis were conducted to determine the molecular epidemiology and evolutionary characteristics. Of these HIV-1-infected patients, 95.6% were male, and men who sex with men (76.7%) were the main transmission route. Only 34.0% of these cases were born in Nanjing, and most of them (64.8%) reported having multiple sex partners in the last 6 months. The maximum likelihood phylogenetic analyses of HIV-1 CRF07_BC revealed two lineages. Overall, 67.3% of Nanjing sequences were connected to at least one other individual distributed in 11 clusters, and the average degree was 21.2 with range (1-178). The clustered patients were more likely to be male. The time to a most recent common ancestor for the early HIV-1 CRF07_BC circulating in Nanjing was estimated to be 1998.71[1997.36-2001.07]. The mean estimated evolutionary rate for the epidemic cluster was slightly lower at 2.38[2.12-2.65] × 10-3 per site per year with the relaxed exponential clock model. HIV-1 CRF07_BC was transmitted into Nanjing more than 20 years ago from Yunnan and has become one of the most predominant subtypes with a higher evolutionary rate than before.

The prevalence of HIV among MSM in China: a large-scale systematic analysis.

BACKGROUND: The prevalence of HIV among men who have sex with men (MSM) has become a significant public health challenge. The aim was to comprehensively estimate the national prevalence of HIV among MSM and its time trends through a large-scale systematic analysis. METHODS: Systematic search of Cochrane Library, PubMed, EMBASE, CNKI, VIP, and Wanfang Data databases without language restriction for studies on the prevalence of HIV among MSM published before Dec.31, 2018. Studies were eligible for inclusion if they were published in the peer-reviewed literature and used validated assessment methods to assess the prevalence of HIV among MSM. Estimates were pooled using random-effects analysis. RESULTS: Data were extracted from 355 cross-sectional studies (571,328 individuals) covered 59 cities from 30 provinces and municipalities of China. The overall national prevalence of HIV among MSM from 2001 to 2018 was estimated to be 5.7% (95% CI: 5.4-6.1%), with high between-study heterogeneity (I2 = 98.0%, P <  0.001). Our study showed an increased tendency in the HIV prevalence as time progressed by meta-regression analysis (I2 = 95.9%, P <  0.0001). HIV prevalence was the highest in those aged 50 years and older with HIV prevalence of 19.3% (95%CI: 13.1-27.4%, N = 13). HIV was more prevalent in the illiterate population (16.8%), than in those who had received an education. Although the internet was a major venue for Chinese MSM seeking male sex partners (35.6, 95%CI: 32.3-39.9%, N = 101), seeking MSM in bathhouses/saunas had the highest associated prevalence of HIV (13.4, 95%CI: 10.3-17.1%, N = 22). The HIV prevalence among MSM varied by location: compared with other regions in China, HIV was highly prevalent among MSM in the southwest (10.7, 95%CI: 9.3-12.2%, N = 91). Compared to participants who sometimes or always used condoms, participants who had never used a condom in the past 6 months had a higher risk of HIV infection, with odds ratios of 0.1 (95%CI: 0.08-0.14). CONCLUSIONS: Our analysis provided reliable estimates of China's HIV burden among MSM, which appears to present an increasing national public health challenge. Effective government responses are needed to address this challenge and include the implementation of HIV prevention.

[Spectrum-activity relationship of trichosanthis fructus and trichosanthis fructus strip pieces for rat myocardial ischemia-reperfusion injury].

To investigate the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. HPLC fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were established, and the values of creatinekinase-MB (CK-MB), myoglobin (MYO) and cardiac troponin-T (cTNT) in 3 dose groups (2.25, 13.5, 27.0 g·kg⁻¹, equivalent to the crude herb g·kg⁻¹) of Trichosanthis Fructus and Trichosanthis Fructus strip pieces with myocardial ischemia-reperfusion injury in rats were measured, and the grey relational analysis was used to study the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. With the dosage increase from 2.25 g·kg⁻¹ to 27.0 g·kg⁻¹, the correlation degree of spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces was also enhanced, but the change trend was different between these two groups. According to the frequency of the top 10 peaks in the correlation degree, peak 17, 14, 16, 19, 32, 12, 26, 30, 4, 6 and 2 were the basic effective substances group of Trichosanthis Fructus, peak 6,14,12,32,30,4 and 6 were the basic effective substances group of Trichosanthis Fructus strip pieces. Peak 6, 14, 12, 32, 30, 4 and 26 in fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were the main common pharmacodynamic substance base, among them, peak 6 was 5-hydroxymethyl furfural, peak 14 was vanillic acid and the peak 28 was rutin, but the correlation degree with the efficacy was different. The effect of Trichosanthis Fructus and Trichosanthis Fructus strip pieces on rat myocardial ischemia-reperfusion injury was due to the synergistic effect of the effective substance groups related to the dosage. The essential pharmacodynamic substance groups of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were different, but they shared a common active ingredient group.

Dual-Labeled Time-Resolved Immunofluorometric Assay for the Simultaneous Quantitative Detection of Hepatitis B Virus Antigens in Human Serum.

In this paper, a novel time-resolved fluorescence immunoassay (TRFIA) is described that allows the simultaneous quantitative detection of hepatitis B virus surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in human serum to aid the diagnosis and monitoring of hepatitis B virus infection. The proposed method was developed based on a two-step sandwich immunoassay protocol in which monoclonal antibodies against HBsAg and HBeAg were co-coated in 96 microtitration wells, then tracer polyclonal antibodies against HBsAg labeled with samarium and tracer monoclonal antibodies against HBeAg labeled with europium chelates were used for detection. The detection range was 0.1-150 IU/mL for HBsAg and 0.5-160 PEIU/mL for HBeAg, and the detection limits were 0.03 IU/L and 0.09 PEIU/ml, respectively. The intra- and inter-assay coefficients of variation were below 8 % for both virus antigens. The dilution linearity and accuracy of the assay were satisfactory. No statistically significant differences were observed in sensitivity or specificity for the serum samples between the dual-label TRFIA and a commercial single-label TRFIA. These results demonstrate that an effective, reliable and convenient HBsAg/HBeAg dual-label TRFIA was successfully developed that may be clinically applicable for blood screening to monitor the course of hepatitis B virus infection and predict treatment responses.

A Simple, Rapid, and Highly Sensitive Electrochemical DNA Sensor for the Detection of α- and ß-Thalassemia in China.

BACKGROUND: Because of the life-consuming treatment and severe consequences associated with thalassemia, it is more effective to prevent than cure thalassemia. Rapid and sensitive detection is critical for controlling thalassemia. In this study, we developed a rapid and accurate test to genotype nondeletional α- and ß-thalassemia mutations by an electrochemical DNA sensor. METHODS: Screen-printed electrodes were used as electrochemical transducers for the sensor, in which the capture probe DNA was attached to the golden surface of the working electrode via an S-Au covalent bond, which is highly suitable for immobilizing the biological element. In addition, two types of ferrocene with varying redox potentials for modified signal probe DNA were adopted. The hybridization signal is detected by alternating current voltammetry when the capture probe and signal probe hybridize with the target DNA. RESULTS: With this technique, 12 types of nondeletional α- and ß-thalassemia mutations were detected, which constitute more than 90% of all the nondeletional types of thalassemia mutation determinants found in China, including the CD142 (TAA>CAA) Constand spring, CD125 (CTG>CCG) Quonsze, CD122 (CAC>CAG) Weastmead, -28 (A>G), Cap+1 (A>C), initiation codon (ATG>AGG), CD17 (AAG>TAG), CD26 (GAG>AAG), CD31(-C), CD41-42 (-CTTT), CD71-72 (+A), and IVS-II-654 (C>T) mutations. Concordance levels were 100% within the 20 blood samples of homozygous wild-type individuals and 238 blood samples of heterozygous mutant individuals. CONCLUSIONS: The electrochemical DNA sensor developed here can be applied for rapid genotyping of thalassemia or other clinical genotyping applications and is useful for early screening of thalassemia in high-risk groups by minimizing the time and investment cost.

Radiological and Clinical Features of Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis(EGPA),also known as Churg-Strauss syndrome,is a clinically rare small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs) and the hypereosinophilic syndromes (HESs),characterized by asthma,disseminated necrotizing vasculitis,extravascular granulomas,peripheral eosinophilia,and tissue eosinophilia. This article reviews the pathology,imaging,and clinical features of EGPA.

Development of a time-resolved fluorescence immunoassay for Epstein-Barr virus nuclear antigen 1-immunoglobulin A in human serum.

Enzyme-linked immunosorbent assay (ELISAs) specific for Epstein-Barr virus nuclear antigen 1 (EBNA1)-immunoglobulin A (IgA) are most commonly used in the clinical diagnosis of EBV infection. But they have a low sensitivity and the enzyme-labeled antibodies are unstable. In this study, a novel immunoassay based on an indirect time-resolved fluoroimmunoassay (TRFIA) was developed. Microtiter plates were coated with recombinant EBNA1. We used Eu(3) (+)-labeled anti-human IgA as probe. The precision, sensitivity, specificity, and stability were evaluated, and comparison with traditional and commercially available ELISAs was also made. The cut-off value for our TRFIA was 2.7. Intra- and inter-assay coefficients of variation for the TRFIA were 1.56-4.99% and 3.92-6.95%, respectively; whereas those for the ELISA were 4.54-8.16% and 7.07-10.52%, respectively. Sensitivity was obviously better than traditional ELISA when diluted positive samples serially. Additionally, stability, specificity test and comparison of sensitivity and specificity between the TRFIA and commercial ELISAs all proved satisfactory. In conclusion, the results demonstrated that EBNA1 IgA TRFIA was a sensitive immunoassay and had potential value in large-scale screening of human serum samples in developing countries.

Development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 IgG antibodies.

Enzyme-linked immunosorbent assays (ELISA) specific for anti-HSV glycoprotein G (gG) are most commonly used in the clinical diagnosis of HSV infection. But most of them are qualitative and with narrow detection ranges. A novel time-resolved fluoroimmunoassay (TRFIA) methodology was developed for the quantitative determination of HSV IgG in human serum. The assay was based on an indirect immunoassay format, and performed in 96-well microtiter plates. HSV-1 and HSV-2 were used as the coating antigens. Eu(3+)-labeled goat anti-(human IgG) polyclonal antibodies were used as tracers. The fluorescence intensity of each well was measured and serum HSV IgG levels quantified against a calibration curve. The detection range of the novel TRFIA was between 5 and 500 AU/mL. Assay sensitivity was 0.568 AU/mL. The intra- and inter-assay coefficients of variation were 0.59-3.63% and 3.65-6.81%, respectively. Analytical recovery, dilution tests and serum panel tests were performed using TRFIA and the results proved satisfactory. There were no statistically significant differences in sensitivity and specificity between the TRFIA and commercial ELISAs. An effective, sensitive and accurate quantitative HSV type 1 and type 2 IgG TRFIA was successfully developed and provided diagnostic value in clinical use.

[Evolution and implementation pathways from desertification prevention and control to sandy land management and use in China]. / 中国从防沙治沙到管沙用沙的演变过程与实现路径.

The construction of ecological civilization emphasizes holistic protection of "mountain-water-forest-farmland-lake-grassland-sand", which has become an important concept of desertification prevention projects in arid and semi-arid areas of China. In the past, sandy land management and use have been neglected in desertification prevention and control, in that the links have not been effectively connected and the long-term and efficient desertification prevention has not been realized. Therefore, combining Qian Xuesen's understanding of "deserticulture", we comprehensively discussed the "long-term achievements" of China's desertification control miracle from the perspective of the historical evolution of the interaction of technology and practice, and the strategic development of policy guidance. Further, we defined the concepts of desertification prevention, desertification control, and sandy land management and use. We analyzed the coupling and coordination relationship between the four links and the scientific principle based on the development of ecological industry chain. Finally, we put forward the policy and market realization pathways, with efficient sandy land management as the core, desertification prevention as the basis, desertification control as the channel, and long-term sandy land use as the foundation. We expected to provide theoretical and practical guidance for creating a new miracle of China's desertification prevention and control.

Comparative analysis of phenolic compounds in different thinned unripe kiwifruits and their biological functions.

Thinned unripe kiwifruits (TUK) are considered the major agro by-products in kiwifruit production. To promote their potential applications, polyphenols and biological effects of unripe fruits from nine commercial kiwifruit cultivars were compared. Our findings showed that TUK were rich in bioactive polyphenols, which varied greatly by different cultivars. Indeed, catechin, epicatechin, procyanidin PB1, procyanidin B2, protocatechuic acid, neochlorogenic acid, and gallic acid were measured as the major phenolic components in most TUK, with the highest levels observed in 'Hongao' and 'Cuiyu' cultivars. Furthermore, TUK exerted strong in vitro antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory activities. Particularly, their stronger antioxidant effects and inhibitory effects on digestive enzymes were probably attributed to their higher contents of phenolic compounds, especially procyanidin B2. Collectively, our findings reveal that TUK are potential resources of valuable polyphenols, which can be exploited as natural antioxidants and natural inhibitors of α-glucosidase and α-amylase.

Characterization, Antioxidant Capacity, and Anti-Inflammatory Activity of Polyphenol-Enriched Extracts Obtained from Unripe, Mature, and Overripe Fruits of Red-Fleshed Kiwifruit Cultivars.

Discarded unripe kiwifruits (DUKs) are regarded as the major agro-byproducts in the production of kiwifruits, which have abundantly valuable secondary metabolites. Nevertheless, owing to the limited knowledge about the differences in phytochemicals and bioactivity between DUKs and mature kiwifruits, the utilization of DUKs in the food industry remains scarce. Hence, to promote their food applications, the phenolic compounds and bioactivity of discarded unripe, mature, and overripe fruits from three red-fleshed kiwifruit cultivars were studied and compared. The results revealed that the levels of total phenolics, total flavonoids, and total procyanidins in kiwifruits varied significantly by maturity stage. In addition, our findings demonstrated that DUKs possessed much higher contents of valuable phenolic compounds (e.g., chlorogenic acid (CHA), neochlorogenic acid (NCHA), gallic acid (GA), protocatechuic acid (PA), procyanidin B1 (ProcB1), procyanidin B2 (ProcB2), procyanidin C1 (ProcC1), quercetin 3-O-glucoside (QueG), and quercetin 3-O-rhamnoside (QueR)) than mature and overripe kiwifruits. Furthermore, DUKs exerted much stronger in vitro antioxidant capacity, inhibitory effects on α-glucosidase, and anti-inflammatory activity than mature and overripe kiwifruits, which were mainly attributed to their higher contents of total polyphenols and individual phenolic components, such as GA, CHA, NCHA, PA, ProcB1, ProcB2, ProcC1, and QueR. Overall, these findings provide sufficient evidence for the development and utilization of DUKs in the food/functional food industry.

Comparison of Protective Effects of Polyphenol-Enriched Extracts from Thinned Immature Kiwifruits and Mature Kiwifruits against Alcoholic Liver Disease in Mice.

Alcoholic liver disease (ALD) is regarded as one of the main global health problems. Accumulated evidence indicates that fruit-derived polyphenols can lower the risk of ALD, this attributed to their strong antioxidant capacities. Thinned immature kiwifruits (TIK) are the major agro-byproducts in the production of kiwifruits, which have abundantly valuable polyphenols. However, knowledge about the protective effects of polyphenol-enriched extract from TIK against ALD is still lacking, which ultimately restricts their application as value-added functional products. To promote their potential applications, phenolic compounds from TIK and their corresponding mature fruits were compared, and their protective effects against ALD were studied in the present study. The findings revealed that TIK possessed extremely high levels of total phenolics (116.39 ± 1.51 mg GAE/g DW) and total flavonoids (33.88 ± 0.59 mg RE/g DW), which were about 7.4 times and 4.8 times greater than those of their corresponding mature fruits, respectively. Furthermore, the level of major phenolic components in TIK was measured to be 29,558.19 ± 1170.58 µg/g DW, which was about 5.4 times greater than that of mature fruits. In particular, neochlorogenic acid, epicatechin, procyanidin B1, and procyanidin B2 were found as the predominant polyphenols in TIK. In addition, TIK exerted stronger in vitro antioxidant and anti-inflammatory effects than those of mature fruits, which was probably because of their higher levels of polyphenols. Most importantly, compared with mature fruits, TIK exhibited superior hepatoprotective effects on alcohol-induced liver damage in mice. The administration of polyphenol-enriched extract from TIK (YK) could increase the body weight of mice, reduce the serum levels of ALP, AST, and ALT, lower the levels of hepatic TG and TC, and diminish lipid droplet accumulation and hepatic tissue damage. In addition, the treatment of YK could also significantly restore the levels of antioxidant enzymes (e.g., SOD and CAT) in the liver and lower the levels of hepatic proinflammatory cytokines (e.g., IL-6, IL-1ß, and TNF-α), indicating that YK could effectively ameliorate ALD in mice by reducing hepatic oxidative stress and hepatic inflammation. Collectively, our findings can provide sufficient evidence for the development of TIK and their extracts as high value-added functional products for the intervention of ALD.

Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity.

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.