Human Visual Pathways for Action Recognition Versus Deep Convolutional Neural Networks: Representation Correspondence in Late But Not Early Layers.

Deep convolutional neural networks (DCNNs) have attained human-level performance for object categorization and exhibited representation alignment between network layers and brain regions. Does such representation alignment naturally extend to other visual tasks beyond recognizing objects in static images? In this study, we expanded the exploration to the recognition of human actions from videos and assessed the representation capabilities and alignment of two-stream DCNNs in comparison with brain regions situated along ventral and dorsal pathways. Using decoding analysis and representational similarity analysis, we show that DCNN models do not show hierarchical representation alignment to human brain across visual regions when processing action videos. Instead, later layers of DCNN models demonstrate greater representation similarities to the human visual cortex. These findings were revealed for two display formats: photorealistic avatars with full-body information and simplified stimuli in the point-light display. The discrepancies in representation alignment suggest fundamental differences in how DCNNs and the human brain represent dynamic visual information related to actions.

Age-varying associations of parent-adolescent relationship and school connectedness with adolescent self-compassion: Differences by gender.

INTRODUCTION: Parent-adolescent relationships and school connectedness are critical promotive factors for adolescent self-compassion. However, little is known about how the magnitude of the associations between these protective factors and self-compassion changes across continuous age groups and whether gender differences exist in the age-varying associations. This study aims to investigate (1) the age-varying associations of parent-adolescent relationships and school connectedness with self-compassion using time-varying effect modeling and (2) how their age-varying associations may differ by gender. METHODS: A total of 14,776 adolescents aged 10-18 (mean age = 13.53 ± 2.08, 52.3% males) from Shenzhen, China participated in this study. All adolescents completed the online questionnaires in the school computer rooms. RESULTS: The results showed that both parent-adolescent relationships and school connectedness were positively associated with adolescent self-compassion, and the magnitudes fluctuated with age. Specifically, the association between parent-adolescent relationships and self-compassion peaked for adolescents in early adolescence, with the key timing for girls (age group of 10 years old) being slightly earlier than boys (age group of 11 years old). The association between school connectedness and self-compassion was stronger for boys in the early years of adolescence (in the age group of 12.7 years), while stronger for girls during middle adolescence (in the age group of 14.0 years). Overall, girls were more sensitive to connections with parents and schools than boys during most age groups. CONCLUSIONS: The findings demonstrated differential key timing for boys and girls regarding family- and school-based intervention to cultivate self-compassion and highlighted the importance of maintaining strong connections with families and schools for cultivating adolescent self-compassion, particularly for girls.

In vivo absorption and excretion in rats and in vitro digestion and fermentation by the human intestinal microbiota of 2-O-ß-D-glucopyranosyl-L-ascorbic acid from the fruits of Lycium barbarum L.

2-O-ß-D-Glucopyranosyl-L-ascorbic acid (AA-2ßG) from Lycium barbarum fruits has diverse bioactivities, yet its absorption and digestion are poorly understood. Therefore, the in vivo absorption of AA-2ßG in rats was investigated in the present study. After oral administration to SD rats, AA-2ßG was absorbed intact, reaching a peak plasma concentration of 472.32 ± 296.64 nM at 90 min, with fecal excretion peaking at 4-8 h and decreasing rapidly by 12-24 h, indicating a prolonged intestinal presence. Furthermore, the digestibility under simulated gastrointestinal conditions and the impact on the gut flora through in vitro fermentation of AA-2ßG were investigated. The results reveal that AA-2ßG resisted in in vitro simulated digestion, indicating potential interactions with the gut microbiota. The results of in vitro fermentation showed that AA-2ßG regulated the composition of the gut microbiota by promoting Oscillospiraceae, Faecalibacterium, Limosilactobacillus, and Fusicatenibacter, while inhibiting Enterococcus, Phocaeicola, Bacteroides, and Streptococcus. Furthermore, at the species level, AA-2ßG promoted the growth of Limosilactobacillus mucosae and Faecalibacterium prausnitzii, and inhibited the growth of Enterococcus. F. prausnitzii is a major producer of n-butyric acid, and the results of short-chain fatty acids also demonstrated a significant promotion of n-butyric acid. Therefore, the study on the absorption, excretion, and regulatory effects of AA-2ßG on the gut microbiota supported its potential development as a functional food additive to enhance intestinal health and prevent diseases.

Exploring the Biogenic Transformation Mechanism of Polyphenols by Lactobacillus plantarum NCU137 Fermentation and Its Enhancement of Antioxidant Properties in Wolfberry Juice.

This study investigated the transformation of polyphenols, including free and bound polyphenols during the fermentation of wolfberry juice by Lactobacillus plantarum NCU137. Results indicated that fermentation significantly increased the free polyphenols content and released bound polyphenols, enhancing the antioxidant activity. Analysis showed that there were 19 free polyphenols, mainly scopoletin, pyrogallol, and dihydroferulic acid, and 16 bound polyphenols, especially p-coumaric acid, feruloyl hexoside, and caffeic acid. A significant correlation was observed between the generation and degradation of polyphenols, and specific bound polyphenols peaked during the 24-48 h fermentation. Furthermore, reduced surface roughness and galacturonic acid content in wolfberry residue, along with increased pectinase activity, suggested substantial pectin degradation in the cell wall, which may be associated with the release of polyphenols, due to pectin serving as carriers for bound polyphenols. The fermentation also increased polyphenol oxidase and peroxidase activity, contributing to polyphenol breakdown. These findings provide insights for improving wolfberry juice production.

Simulated gastrointestinal digestion of two different sources of biodegradable microplastics and the influence on gut microbiota.

Biodegradable plastics, were considered environmentally friendly, may produce more microplastic particles (MPs) within the same period and exert more pronounced adverse effects on human health than traditional non-biodegradable plastics. Thus, this study investigated the changes of two kinds of biodegradable MPs from different sources in the digestive tract by using simulated digestion and fermentation models in vitro, with particle size, scanning electron microscopy (SEM) and gel permeation chromatography (GPC) analysis, and their implications on the gut microbiota were detected by full-length bacterial 16S rRNA gene amplicon sequencing. Poly(ε-caprolactone) (PCL) MPs exhibited stability in the upper gastrointestinal tract, while poly(lactic acid) (PLA) MPs were degraded beginning in the small intestine digestion phase. Both PCL and PLA MPs were degraded and oligomerized during colonic fermentation. Furthermore, this study highlighted the disturbance of the gut microbiota induced by MPs and their oligomers. PCL and PLA MPs significantly changed the composition and reduced the α-diversity of the gut microbiota. PCL and PLA MPs exhibited the same inhibitory effects on key probiotics such as Bifidobacterium, Lactobacillus, Faecalibacterium, Limosilactobacillus, Blautia, Romboutsia, and Ruminococcus, which highlighted the potential hazards of these materials for human health. In conclusion, this study illuminated the potential biodegradation of MPs through gastrointestinal digestion and the complex interplay between MPs and the gut microbiota. The degradable characteristic of biodegradable plastics may cause more MPs and greater harm to human health.

Psychodynamic profiles of major depressive disorder and generalized anxiety disorder in China.

Traditional clinical diagnoses relying on symptoms may overlook latent factors that illuminate mechanisms and potentially guide treatment. The Operationalized Psychodynamic Diagnosis (OPD) system may compensate for symptom-based diagnosis by measuring psychodynamic profiles underlying mental disorders through conflicts and structure axes. However, OPD has not been widely adopted in China, and it remains unclear whether OPD can be used as an effective approach to distinguish between depression and anxiety. The current study aims to adopt the OPD system to investigate the psychodynamic profiles of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in China, targeting patients with "pure" symptoms without comorbidity. We recruited 42 MDD patients, 32 GAD patients, and 31 healthy controls (HC), and assessed their self-report depression and anxiety symptoms, along with their underlying psychodynamic profiles through OPD interviews. Overall, both MDD and GAD patients showed more prominent conflict issues and lower levels of structure than HC. The MDD and GAD groups yielded different conflict profiles and conflict processing modes when processing their second conflicts. Importantly, the multi-dimensional psychodynamic profiles achieved machine learning classification of clinical groups with an accuracy of 0.84, supporting successful distinction of MDD and GAD patients. In conclusion, the OPD demonstrated sensitivity in revealing distinct psychodynamic profiles underlying "pure" depression and anxiety clinical populations in China. This work calls for future incorporation of OPD as a tool to investigate psychodynamic formulations underlying mental disorders, compensating for traditional symptom-based diagnostic approaches to guide precise individualized interventions.

RNAi silencing CHS1 gene shortens the mortality time of Plutella xylostella feeding Bt-transgenic Brassica napus.

BACKGROUND: Insect-resistance genetically modified (GM) plants derived from Bacillus thuringiensis (Bt) have been cultivated to control pests, but continuous cultivation of Bt-transgenic plants at large-scale regions leads to the resistance evolution of target insects to transgenic plants. RNA interference (RNAi) technology is considered an effective strategy in delaying the resistance evolution of target insects. RESULTS: We here developed a single transgenic oilseed rape (Brassica napus) line with hairpin RNA of the chitin-synthase 1 gene (CHS1) of Plutella xylostella (hpPxCHS1) and a pyramid transgenic B. napus line harboring hpPxCHS1 and Bt gene (Cry1Ac). Escherichia coli HT115 delivered hpPxCHS1 showed negative effects on the growth of P. xylostella. The single transgenic and pyramid transgenic B. napus significantly reduced the larval weight and length of P. xylostella and increased its lethality rate, with down-regulation expression of the PxCHS1 gene in insects. CONCLUSION: Compared to Bt-transgenic B. napus, pyramid-transgenic B. napus shorted the mortality time of P. xylostella, indicating that RNAi technology synergistic with Bt protein improves the effectiveness of controlling target insects. Our results proved that RNAi can delay the resistance evolution of target insects to Bt-transgenic plants. © 2024 Society of Chemical Industry.

Patterns of saliency and semantic features distinguish gaze of expert and novice viewers of surveillance footage.

When viewing the actions of others, we not only see patterns of body movements, but we also "see" the intentions and social relations of people. Experienced forensic examiners - Closed Circuit Television (CCTV) operators - have been shown to convey superior performance in identifying and predicting hostile intentions from surveillance footage than novices. However, it remains largely unknown what visual content CCTV operators actively attend to, and whether CCTV operators develop different strategies for active information seeking from what novices do. Here, we conducted computational analysis for the gaze-centered stimuli captured by experienced CCTV operators and novices' eye movements when viewing the same surveillance footage. Low-level image features were extracted by a visual saliency model, whereas object-level semantic features were extracted by a deep convolutional neural network (DCNN), AlexNet, from gaze-centered regions. We found that the looking behavior of CCTV operators differs from novices by actively attending to visual contents with different patterns of saliency and semantic features. Expertise in selectively utilizing informative features at different levels of visual hierarchy may play an important role in facilitating the efficient detection of social relationships between agents and the prediction of harmful intentions.

Non-IL-2-blocking anti-CD25 antibody inhibits tumor growth by depleting Tregs and has synergistic effects with anti-CTLA-4 therapy.

CD25, also known as the interleukin-2 receptor α chain (IL-2Rα), is highly expressed on regulatory T cells (Tregs), but relatively lower on effector T cells (Teffs). This makes it a potential target for Treg depletion, which can be used in tumor immunotherapy. However, marketed anti-CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL-2 binding to CD25 on Teffs, which in turn destroys the function of Teffs. Recent studies have shown that non-IL-2-blocking anti-CD25 antibodies have displayed exciting antitumor effects. Here, we screened out a non-IL-2-blocking anti-CD25 monoclonal antibody (mAb) 7B7 by hybridoma technology, and confirmed its antitumor activity via depleting Tregs in a CD25 humanized mouse model. Subsequently, we verified that the humanized 7B7, named as h7B7-15S, has comparable activities to 7B7, and that its Treg depletion is further increased when combined with anti-CTLA-4, leading to enhanced remodeling of the tumor immune microenvironment. Moreover, our findings reveal that the Fab form of h7B7-15S has the ability to deplete Tregs, independent of the Fc region. Taken together, our studies expand the application of anti-CD25 in tumor immunotherapy and provide insight into the underlying mechanism.

Palmitoleic acid-rich oleaginous yeast Scheffersomyces segobiensis DSM 27193 exerts anti-obesity effects by ameliorating hepatic steatosis and adipose tissue hypertrophy.

BACKGROUND: Yeast biomass, encompassing fatty acids, terpenoids, vitamins, antioxidants, enzymes, and other bioactive compounds have been extensively utilized in food-related fields. The safety and potential bioactivities of Scheffersomyces segobiensis DSM 27193, an oleaginous yeast strain, are unclear. RESULTS: Scheffersomyces segobiensis DSM 27193 accumulated large palmitoleic acid (POA) levels (43.4 g kg-1 biomass) according to the results of whole-cell components. We annotated the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and predicted the categories and host of the pathogen-host interactions (PHI) genes in S. segobiensis DSM 27193. However, S. segobiensis DSM 27193 did not exert toxic effects in mice. Administration of S. segobiensis DSM 27193 led to substantial weight reduction by diminishing food intake in an obesity mouse model. Additionally, it reversed hepatic steatosis and adipose tissue hypertrophy, and improved abnormalities in serum biochemical profiles such as triglyceride, total cholesterol, low-density lipoprotein cholesterol, lipopolysaccharide, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. CONCLUSION: This study is the first to illustrate the safety and effects of S. segobiensis DSM 27193 against obesity and offers a scientific rationale for its application in functional food supplements. © 2023 Society of Chemical Industry.

Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling.

Introduction: Threat learning and extinction processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on a priori regions of interest, owing partly to the ease of translating between these regions in human and non-human animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics during threat learning is essential for understanding the neuropathology of fear-related disorders in humans. Methods: 223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat conditioning. Connectivity networks were tested to see how they responded to conditional stimuli during early and late phases of threat acquisition and extinction and during early trials of extinction recall. Results: A network overlapping with the default mode network involving hippocampus, vmPFC, and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dACC, mPFC, and inferior frontal gyrus was implicated in threat acquisition and extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and fronto-parietal networks were involved in the acquisition or extinction of learned threat responses. Conclusions: These findings help confirm previous investigations of specific brain regions in a model-free fashion and introduce new findings of spatially independent networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel coordinating different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.

Intracellular Polysaccharides of Aspergillus cristatus from Fuzhuan Brick Tea Leverage the Gut Microbiota and Repair the Intestinal Barrier to Ameliorate DSS-Induced Colitis in Mice.

The intracellular polysaccharides of Aspergillus cristatus (IPSs) from Fuzhuan brick tea have been demonstrated to improve immune function linked to modulating the gut microbiota. Herein, to further investigate the efficacy of IPSs to maintain gut homeostasis, the protection of the purified fraction of IPSs (IPSs-2) on the mice with colitis induced by dextran sulfate sodium (DSS) and the underlying mechanisms were explored in this study. The results revealed that IPSs-2 alleviated the typical symptoms of colitis and suppressed the excessive inflammatory mediators, regulating the genes related to inflammatory responses in the colon at the mRNA level. Meanwhile, IPSs-2 treatment reinforced the intestinal barrier function by ameliorating the DSS-induced histological injury, facilitating the differentiation of goblet cells to enhance Mucin-2 generation, and enhancing the expression of tight junction proteins to alleviate colitis. In addition, IPSs protected against colitis by promoting the production of short-chain fatty acids (SCFAs), the activation of SCFAs receptors, and the leverage of the gut microbiota via the enrichment of Bacteroides, Parabacteroides, Faecalibacterium, Flavonifractor_plautii, and Butyricicoccus, linking with reducing inflammation and repairing intestinal barrier function. Overall, our research revealed the therapeutic potential of IPSs-2 as a prebiotic for attenuating inflammatory bowel disease and provided a rationale for future investigation.

Anthocyanins from Lycium ruthenicum Murray Ameliorated High-Fructose Diet-Induced Neuroinflammation through the Promotion of the Integrity of the Intestinal Barrier and the Proliferation of Lactobacillus.

In the present study, we found that anthocyanins from Lycium ruthenicum Murray (ACN) potently ameliorated a high-fructose diet (HFrD)-induced neuroinflammation in mice. ACN improved the integrity of the intestinal barrier and suppressed the toll-like receptor 4 (TLR4) signaling pathway to ameliorate the neuroinflammation, which was verified by Tlr4-/- mice. Furthermore, ACN could modulate the HFrD-induced dysbiosis of gut microbiota. The fecal microbiota transplantation from ACN-induced mice was sufficient to attenuate the neuroinflammation, while the amelioration of neuroinflammation by ACN was blocked upon gut microbiota depletion. In addition, ACN-induced increment of the relative abundance of Lactobacillus might be responsible for the alleviation of the neuroinflammation, which was further confirmed in the promoting effect of ACN on the growth of Lactobacillus in vitro. Overall, these results provided the evidence of a comprehensive cross-talk mechanism between ACN and neuroinflammation in HFrD-fed mice, which was mediated by reducing gut microbiota dysbiosis and maintaining the intestinal barrier integrity.

Effects of long-term administration of theasinensin A on healthy C57BL/6J mice: Enhancing the function of epididymal white adipose tissue and regulating the colonic microenvironment.

The effects of theasinensin A (TSA) on healthy C57BL/6J mice were investigated. Results showed that long-term administration of 100 mg/kg body weight/day TSA might be non-toxic to healthy mice based on the unaltered basal biochemical indicators related to glucose and lipid metabolism, inflammatory factors and hepatic injury. On the contrary, TSA stimulated the rate of lipid turnover and browning of white adipose tissues, accelerated the adipocytic energy mobilization, and then reduced the white adipocytic size, ultimately enhancing resistance to obesity in healthy mice. Furthermore, TSA not only up-regulated the expression of mucin, tight junction protein, and short-chain fatty acids receptor, but also regulated the intestinal microbiota by enhancing the typical beneficial microbe Akkermansia muciniphila, thereby modulating the colonic microenvironment. These results suggested that TSA had a potential strengthening effect on the resistance of healthy mice to metabolic disorders, which provides a theoretical basis for the utilization of TSA.

Threat Neurocircuitry Predicts the Development of Anxiety and Depression Symptoms in a Longitudinal Study.

BACKGROUND: Owing to high heterogeneity and comorbidity, the shared and unique neural mechanisms underlying the development of anxiety and major depressive disorders remain unclear. Using a dimensional model describing shared versus unique symptoms associated with anxiety and depression, this study investigated how longitudinal changes in symptom dimensions relate to threat neurocircuitry. METHODS: Participants were 18- to 19-year-olds (N = 279, 186 females) who completed self-report measures of anxiety and depression at baseline and at 10, 20, and 30 months. Linear slopes of symptom dimensions of general distress, fear, and anhedonia-apprehension were estimated through a trilevel factorial model. In addition, functional magnetic resonance imaging scans were obtained while participants performed Pavlovian fear conditioning tasks at baseline and 30 months, including three phases of fear acquisition, extinction, and extinction recall. Neural responses in regions of interest related to threat neural circuitry (e.g., amygdala, ventromedial prefrontal cortex, and subgenual anterior cingulate cortex) were extracted. RESULTS: Linear mixed models used to estimate relationships between changes of symptom dimensions and neural responses revealed two major findings: 1) greater neural responses to threatening stimuli during fear acquisition at baseline were associated with a greater increase in fear symptoms during the 30-month prospective period; and 2) elevated neural responses to the extinguished stimulus during extinction recall at 30 months were negatively associated with changes in general distress, suggesting that greater increases in general distress are associated with larger deficits in extinction memory. CONCLUSIONS: These findings improve our understanding of pathophysiological pathways underlying the development of anxiety and depression, while separating symptom dimensions that are shared versus unique between the two disorders.

A critical review of Fuzhuan brick tea: processing, chemical constituents, health benefits and potential risk.

Fuzhuan brick tea (FBT) is a traditional popular beverage in the border regions of China. Nowadays, FBT has been attracted great attention due to its uniquely flavor and various health-promoting functions. An increasing number of efforts have been devoted to the studies on health benefits and chemistry of FBT over the last decades. However, FBT was still received much less attention than green tea, oolong tea and black tea. Therefore, it is necessary to review the current encouraging findings about processing, microorganisms, chemical constituents, health benefits and potential risk of FBT. The fungus fermentation is the key stage for processing of FBT, which is involved in a complex and unique microbial fermentation process. The fungal community in FBT is mainly dominated by "golden flower" fungi, which is identified as Aspergillus cristatus. A great diversity of novel compounds is formed and identified after a series of biochemical reactions during the fermentation process of FBT. FBT shows various biological activities, such as antioxidant, anti-inflammatory, anti-obesity, anti-bacterial, and anti-tumor activities. Furthermore, the potential risk of FBT was also discussed. It is expected that this review could be useful for stimulating further research of FBT.

CD25: A potential tumor therapeutic target.

CD25 is the alpha-chain of the heterotrimer IL-2 receptor. CD25 is expressed on the surface of both immune and non-immune cells with different frequencies. For cancers, CD25 is expressed at high levels in many types of hematological malignancies, but at low levels in most solid tumors. CD25 is also highly expressed in activated circulating immune cells and regulatory T cells (Tregs). Infiltration of Tregs in the tumor microenvironment can lead to an imbalanced ratio of effector T cells (Teffs) and Tregs, which is associated with the progression of cancers. A rescued Teff/Treg cell ratio indicates an efficient anti-tumor response to immunotherapy. CD25 as a potential target for the depletion of Tregs is critical in developing new immunotherapeutic strategies. Few articles have summarized the relationships between CD25 and tumors, or the recent progress of drugs targeting CD25. In this paper, we will discuss the structures of IL-2 and IL-2R, the biological function of CD25 and its important role in tumor therapy. In addition, the latest research on drugs targeting CD25 has been summarized, providing guidance for future drug development.

Fluoride induced leaky gut and bloom of Erysipelatoclostridium ramosum mediate the exacerbation of obesity in high-fat-diet fed mice.

INTRODUCTION: Fluoride is widely presented in drinking water and foods. A strong relation between fluoride exposure and obesity has been reported. However, the potential mechanisms on fluoride-induced obesity remain unexplored. Objectives and methods The effects of fluoride on the obesity were investigated using mice model. Furthermore, the role of gut homeostasis in exacerbation of the obesity induced by fluoride was evaluated. Results The results showed that fluoride alone did not induce obesity in normal diet (ND) fed mice, whereas, it could trigger exacerbation of obesity in high-fat diet (HFD) fed mice. Fluoride impaired intestinal barrier and activated Toll-like receptor 4 (TLR4) signaling to induce obesity, which was further verified in TLR4-/- mice. Furthermore, fluoride could deteriorate the gut microbiota in HFD mice. The fecal microbiota transplantation from fluoride-induced mice was sufficient to induce obesity, while the exacerbation of obesity by fluoride was blocked upon gut microbiota depletion. The fluoride-induced bloom of Erysipelatoclostridium ramosum was responsible for exacerbation of obesity. In addition, a potential strategy for prevention of fluoride-induced obesity was proposed by intervention with polysaccharides from Fuzhuan brick tea. Conclusion Overall, these results provide the first evidence of a comprehensive cross-talk mechanism between fluoride and obesity in HFD fed mice, which is mediated by gut microbiota and intestinal barrier. E. ramosum was identified as a crucial mediator of fluoride induced obesity, which could be explored as potential target for prevention and treatment of obesity with exciting translational value.

Design, Synthesis, and Bioevaluation of a Novel Hybrid Molecular Pyrrolobenzodiazepine-Anthracenecarboxyimide as a Payload for Antibody-Drug Conjugate.

A novel series of hybrid molecules combining pyrrolobenzodiazepine (PBD) and anthracenecarboxyimide pharmacophores were designed, synthesized, and tested for in vitro cytotoxicity against various cancer cell lines. The most potent compound from this series, 37b3, exhibited a subnanomolar level of cytotoxicity with an IC50 of 0.17-0.94 nM. 37b3 induced DNA damage and led to tumor cell cycle arrest and apoptosis. We employed 37b3 as a payload to conjugate with trastuzumab to obtain the antibody-drug conjugate (ADC) T-PBA. T-PBA maintained its mode of target and internalization ability of trastuzumab. We demonstrated that T-PBA could be degraded through the lysosomal pathway to release the payload 37b3 after internalization. T-PBA showed a powerful killing effect on Her2-positive cancer cells in vitro. Furthermore, T-PBA significantly inhibited tumor growth in gastric and ovarian cancer xenograft mouse models without overt toxicity. Collectively, these studies suggest that T-PBA represents a promising new ADC that deserves further investigation.

Fuzhuan brick tea polysaccharides serve as a promising candidate for remodeling the gut microbiota from colitis subjects in vitro: Fermentation characteristic and anti-inflammatory activity.

The purified fraction 3 of polysaccharides from Fuzhuan brick tea (FBTPS-3) could attenuate the colitis and modulate the gut microbiota. However, the relationship between anti-inflammatory effect of FBTPS-3 and the gut microbiota is still unknown. Thus, the anaerobic fermentation in vitro was used to investigate the potential mechanism. FBTPS-3 could be utilized and degraded by gut microbiota from inflammatory bowel disease (IBD) subjects. Furthermore, FBTPS-3 could modulate the composition and structure of IBD gut microbiota toward to that of healthy group. FBTPS-3 showed a superior modulated effect on IBD gut microbiota by increasing Bacteroides and decreasing Escherichia/Shigella. Furthermore, the fermentation solution rather than FBTPS-3 itself showed anti-inflammatory effects on lipopolysaccharide-treated RAW264.7 macrophages, which might be due to the metabolites such as short-chain fatty acids (SCFAs). Thus, FBTPS-3 can be expected as novel prebiotics for treatment of IBD via modulating gut microbiota, and promoting the production of SCFAs.