Soy Peptide Supplementation Mitigates Undernutrition through Reprogramming Hepatic Metabolism in a Novel Undernourished Non-Human Primate Model.

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

Synthetic Biomimetic Liposomes Harness Efferocytosis Machinery for Highly Efficient Macrophages-Targeted Drug Delivery to Alleviate Inflammation.

Macrophages play pivotal roles in the regulation of inflammatory responses and tissue repair, making them a prime target for inflammation alleviation. However, the accurate and efficient macrophages targeting is still a challenging task. Motivated by the efficient and specific removal of apoptotic cells by macrophages efferocytosis, a novel biomimetic liposomal system called Effero-RLP (Efferocytosis-mediated Red blood cell hybrid Liposomes) is developed which incorporates the membrane of apoptotic red blood cells (RBCs) with liposomes for the purpose of highly efficient macrophages targeting. Rosiglitazone (ROSI), a PPARγ agonist known to attenuate macrophage inflammatory responses, is encapsulated into Effero-RLP as model drug to regulate macrophage functions in DSS-induced colitis mouse model. Intriguingly, the Effero-RLP exhibits selective and efficient uptake by macrophages, which is significantly inhibited by the efferocytosis blocker Annexin V. In animal models, the Effero-RLP demonstrates rapid recognition by macrophages, leading to enhanced accumulation at inflammatory sites. Furthermore, ROSI-loaded Effero-RLP effectively alleviates inflammation and protects colon tissue from injury in the colitis mouse model, which is abolished by deletion of macrophages from mice model. In conclusion, the study highlights the potential of macrophage targeting using efferocytosis biomimetic liposomes. The development of Effero-RLP presents novel and promising strategies for alleviating inflammation.

Infantile hemangioma in a subadult Chinese pangolin: a case report.

BACKGROUND: Hemangiomas are a relatively common type of tumor in humans and animals. Various subtypes of hemangiomas have been described in the literature. The classification methods for hemangiomas differ between human and veterinary medicine, and the basis for tumor classification can be found in the literature. CASE PRESENTATION: This study describes a tumor in the subcutaneous tissue of the right dorsum of an artificially rescued juvenile Chinese pangolin. Computed tomography (CT) examination yielded the preliminary diagnosis of a vascular malformation, and surgery was performed to resect the tumor. Histopathological examination showed that the tumor mainly was consisted of adipose tissue, capillaries, and spindle cells in the fibrous stroma. Immunohistochemistry showed the positive expression of CD31, CD34, α-SMA, GLUT1 and WT-1 in the tumor tissue, and the tumor was eventually diagnosed as an infantile haemangioma. CONCLUSION: The final diagnosis of infantile hemangioma was depended on the histopathological immunohistochemical and CT examination of the neoplastic tissue. This is the first report of infantile hemangioma in a critically endangered species Chinese pangolin.

Gamma Rhythm and Theta-gamma Coupling Alternation in Chronic Unpredictable Stress (CUS)-induced Depression Rats.

Depression is a debilitating disease, which, in severe cases, can lead to suicide. However, objective and reliable biomarker for the diagnosis of depression is lack. In this preclinical study, we recorded resting local field potentials (LFPs) from chronic unpredictable stress (CUS)-induced depressed (n =20) and control (n = 20) rats and then compared their gamma activities in terms of single-band and cross-frequency coupling patterns. Both theta-gamma coupling and relative power in total gamma band revealed significant abnormalities in gamma rhythm in the right auditory cortex of depressed rats. These findings implied that resting-state gamma rhythms may be a promising objective diagnostic biomarker for depression. Furthermore, our research provided direct evidence from the perspective of source signals in deep brain sites, which might be useful for clinical applications.Clinical Relevance- This research showed that resting gamma in the auditory cortex is a promising biomarker for depression diagnosis.

Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation.

Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage-mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3-associated phagocytosis (LAP), a non-canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G-protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL-induced efferocytosis, anti-colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3-associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.

Cost-effective colorimetric sensor for authentication of protected designation of origin (PDO) Longjing green tea.

Traceability and authentication of protected designation of origin (PDO) tea is an important prerequisite to safeguard its production and distribution system. Here, indicator displacement array (IDA) sensors consisting of natural anthocyanidins and edible metal ions were developed to authenticate PDO and non-PDO Longjing from different origins. Five IDA elements were selected for constructing sensors, achieved by an indicator displacement reaction after adding epigallocatechin gallate solution. The obtained sensors were subsequently used for real tea samples. Unsupervised algorithms were used for data exploration among PDO and non-PDO teas. The supervised support vector machine (SVM) model further achieved accurate authentication of PDO and non-PDO Longjing with a correct classification rate of 100% for the 26 validated samples. The developed IDA sensor thus achieves accurate authentication of PDO tea in a hazard-free and cost-efficient way, providing a useful tool for origin authentication of other agricultural products.

Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear pathogenesis, the current therapeutic strategy for IBD is focused on symptoms alleviation. Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis. Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms, including modulating macrophage function. Macrophages are the gatekeepers of intestinal immune homeostasis, especially involved in regulating inflammation remission and tissue repair. Interestingly, many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function, suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation. Here, we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance, inflammation remission and tissue repair regulation in IBD, and discuss how this knowledge can be used as a strategy for IBD treatment.

Indicator displacement assay for freshness monitoring of green tea during storage.

Aging of green tea leads to reductions in its flavor and health value, yet in situ testing methods for green tea freshness are lacking. A novel sensitive indicator displacement assay (IDA) sensor was constructed and applied for monitoring of green tea freshness during storage. Low-cost pH dyes and metal ions were used as indicators and receptors, respectively, for the targeted detection of catechins in tea samples. The feasibility of the IDA reaction was verified using images and UV-vis spectroscopy, respectively. IDA combined with supervised algorithms achieved accurate identification of green tea freshness with an accuracy of 86.67%, and acceptable accuracies in the prediction of catechin monomers and total catechins with ratio of prediction to deviation values over 1.5. Thus, the developed IDA sensor is capable of qualitative and quantitative monitoring of the green tea freshness during storage, providing a new option for quality evaluation and control of green teas.

Gamma auditory steady-state response as a promising electrophysiological biomarker for depression: an in vivo study with chronic unpredictable mild stress (CUS)-induced rats.

Gamma oscillations play a functional role in brain cognitions. Recently, auditory steady-state response (ASSR) has been reported abnormally in depression clinically, particularly in the low-gamma band. However, clinical electroencephalography research has challenges obtaining pure signals straight from the source level, making information isolation and precise localization difficult. Besides, the ASSR deficits pattern remains unclear. Herein, we focused on the origin of ASSR-primary auditory cortex (A1), the central node in the auditory pathway. We assessed the evoked-power and phase-synchronization using local field potentials (LFP) in depression (n = 21) and control (n = 22) rats. Subsequent processing of the received auditory information was examined using event-related potentials (AEPs). Results showed that depressed rats exhibited significant gamma ASSR impairments in peak-to-peak amplitude, inter-trial phase coherence, and signal-to-noise ratio. These deficits were more pronounced during 40-Hz auditory stimuli in right-A1, indicating severe gamma network abnormalities in the right auditory pathway. Besides, increased N2 and P3 amplitudes in depression group were found, indicating excessive inhibitory control and contextual processing. Taken together, these ASSR abnormalities have a high specificity of more than 90% and high sensitivity of more than 80% to distinguish depression under 40-Hz auditory stimuli. Our findings provided an abnormal gamma network in the auditory pathway, as a promising diagnostic biomarker in the future.

An all-solid-state photo-rechargeable battery based on Cs3Bi2I9.

Here, we present a new two-electrode photo-rechargeable FTO/TiO2/Cs3Bi2I9/Pt/FTO system. The key material is the photoactive lead-free perovskite Cs3Bi2I9, which performs photoelectric conversion and provides energy storage. This study is the first example of a battery system in which charging and discharging are based on bismuth redox chemistry. In the photo-charged state, the fabricated battery has an open-circuit voltage of ∼0.28 V in the dark. With a series-connected pack of these batteries, an LED was lit for tens of seconds in the dark.

Hericium erinaceus mycelium-Derived Polysaccharide Alleviates Ulcerative Colitis and Modulates Gut Microbiota in Cynomolgus Monkeys.

SCOPE: Ulcerative colitis (UC) is rapidly increasing worldwide but prolong use of available corticosteroids treatment is associated with numerous adverse effects. There is the urgent need to develop novel therapeutic options. However, this requires the use of suitable disease models, but current models are generated with chemical agents mainly in rodents, which are unable to recapitulate the human occurrence. The aim of this study is to validate the occurrence of spontaneous UC in cynomolgus monkeys and explore the potential of Hericium erinaceus mycelium-derived polysaccharide in reversing UC pathologies. METHODS AND RESULTS: Postmortem bowel evaluation and biochemical analysis including inflammatory markers and fecal occult blood testing (FOBT) as well as nutrition status parameters, confirm the non-artificial induced spontaneous occurrence of UC in cynomolgus monkeys. Subsequently, H. erinaceus mycelium-derived polysaccharide supplementation significantly attenuates UC pathologies, improves nutritional status, reduces the incidence of diarrhea, and reduces inflammation in UC monkeys. Importantly, the polysaccharides administration enhances intestinal function and reshapes the gut microbiota. CONCLUSION: The study confirms the spontaneous UC monkeys can closely mimic the occurrence of UC in humans. Moreover, H. erinaceus mycelium-derived polysaccharide can effectively restore UC in monkeys, which show the prospects as precision nutritional supplement for the management of UC.

Visualizing chemical indicators: Spatial and temporal quality formation and distribution during black tea fermentation.

Fermentation is a key black tea processing step and makes an important contribution to quality formation. Current approaches to fermentation monitoring are costly or laboratory-based. Here, we first evaluated the potential of at-line computer vision for detecting fermentation quality in a tea factory. A self-built industrial camera was used to collect tea samples at various fermentation durations. The correlations of color variables that were extracted from the images with key quality indicators in the tea samples were verified. Subsequently, partial least-squares regression models based on the color variables showed high prediction accuracy with residual prediction deviation values of 4.13, 3.53, and 3.39 for catechins, theaflavins and chlorophylls, respectively. Finally, the spatial and temporal distributions of indicators during fermentation were mapped to visualize the fermentation quality. This study realized low-cost, at-line and real-time detection for black tea fermentation, which provides technical support for the industrial and intelligent production of black tea.

Cost-effective and sensitive indicator-displacement array (IDA) assay for quality monitoring of black tea fermentation.

Herein, a new indicator-displacement array (IDA) sensor was developed for the quality evaluation of black tea fermentation. On the principle of the reversible covalent binding of phenylboronic acid and catechol, phenylboronic acids were selected as acceptors for targeted binding to polyphenols. Pyrocatechol violet and alizarin red S were used as indicators of the reaction. The IDA sensors have sensitive differential responses to fermented tea samples, achieving an assessment of the fermentation degree with accuracies of 80.39-88.00% by support vector machine (SVM). In addition, the key polyphenol components of the fermentation process were accurately predicted by the IDA and SVM regression with ratio of prediction to deviation values of 1.55-1.72, 2.03-2.21, and 2.03-2.08 for total polyphenols, total catechins, and epigallocatechin-3-O-gallate, respectively. In conclusion, the developed IDA sensor is capable of the in-situ quality monitoring of black tea fermentation, with the advantages being cost-effectiveness, sensitivity, and rapidity.

pH indicator-based sensor array in combination with hyperspectral imaging for intelligent evaluation of withering degree during processing of black tea.

Withering is one of the most critical steps in the processing of black tea. The degree of withering affects the aroma quality of the finished tea. In this study, we used a pH indicator-based colorimetric sensor array in combination with hyperspectral imaging to intelligently evaluate the withering degree. After analyzing the difference between images taken before and after the reaction of pH indicators with withered leaves, six pH indicators were selected to build a sensor array. Then, the hyperspectral image of each pH indicator was obtained at wavelengths between 400 and 1000 nm. Nonlinear support vector machine (SVM) and least-squares (LS) SVM models were established to determine the degree of withering. Results revealed that the spectral information from single pH indicator failed to accurately evaluate the withering degree. The LS-SVM model achieved satisfactory discriminant results with the low-level data fusion of six pH indicators followed by principal component analysis for dimensionality reduction. The optimal model yielded accuracies of 93.75% and 90.00% for the calibration and prediction sets, respectively. The results indicated that colorimetric sensor array in combination with hyperspectral imaging can effectively determine the withering degree, thus providing a novel method for the intelligent processing of food and tea.

Elastic net-based identification of GAMT as potential diagnostic marker for early-stage gastric cancer.

Early-stage gastric cancer (GC) is asymptomatic. How to diagnose the early-stage GC is challenging. The sensitivity and specificity of diagnosing signatures for early-stage patients are still poor. Elastic-net-based analysis was used to identify potential diagnostic signatures of early-stage GC. The expression level of candidate gene was evaluated by immunohistochemistry staining. The potential function of candidate gene was verified by overexpressing in vitro. Consensus genes (including GAMT) were identified using the different strengths of the penalty. Surprisingly, GAMT was still identified even if some multicollinear variables were deleted directly. IHC staining showed that there are no GAMT-positive signals in the cell nuclei of all tumor tissues, while GAMT does express in nuclei of adjacent normal tissue. There are 16.33% positive cell nuclei in paracancerous tissues. In addition, the number of larger-area colonies of overexpression-GAMT group, empty-vector group, and AGS group is 70±29.21, 151.33±15.95, and 111.67±22.03, respectively. Number of larger colonies in group with overexpression of GAMT is significantly less than control groups. Elastic-net-penalty-based workflow is a effective tool to identify diagnostic biomarker for early-stage solid tumor. GAMT has strong potential to be the diagnostic biomarker for the early-stage GC.

Effect of oral and intraperitoneal administration of walnut-derived pentapeptide PW5 on cognitive impairments in APPSWE/PS1ΔE9 mice.

Food-derived bioactive peptides, encrypted in native protein sequence, have attracted enormous research attention due to its potential in the prevention and/or treatment of a broad range of diseases. However, administration route poses a great challenge to their development and commercial applications. Patient-friendly delivery of bioactive peptides which also enhances its efficacy urgently remain to be addressed. Here we compared the effects of oral administration (PO) to intraperitoneal injection (IP) of a walnut-derived bioactive pentapeptide PW5 (Pro-Pro-Lys-Asn-Trp) in cognitive improvement capacity in APPSWE/PS1ΔE9 transgenic mice. Strikingly, we found that only PO administration of PW5 could effectively ameliorate cognitive impairments and reduce the ß-amyloid deposits in the brain compared to the IP administration. This may be attributable to alterations in the gut microbiota communities, including alterations in microbial α- and ß-diversities after PO treatment, leading to the reversal of the relative abundances of ten differential genera (e.g. Acinetobacter, Lactobacillus, Akkermansia, Allobaculum, Adlercreutzia, Coriobacteriaceae, unclassified_p_ Firmicutes, Desulfovibrionaceae, Oscillospira and Anaeroplasma) which are highly correlated with disease progression. Thus, this study has leveraged on PW5 to proof the superior efficacy of oral delivery to injection delivery in improving cognitive impairments in vivo, suggesting that oral delivery might be highly recommended as a prioritized delivery route in the development of food-derived peptides.

Modulating emotion processing using transcranial alternating current stimulation (tACS) - A sham-controlled study in healthy human participants.

As an emerging non-invasive neuromodulation technique, transcranial alternating current stimulation(tACS) has been reported to be used in mood regulation, cognitive modulation and brain trauma recovery by applying specific frequency currents. However, the neuromodulatory mechanisms and effects of tACS on emotion processing are unclear. In this study, a single-blind experiment with 44 healthy subjects in 1:1 randomized groups (experimental group given 10 Hz-tACS and control group given sham-stimulation) was conducted. The effects of tACS applied to the prefrontal lobe on the brain's emotional state and emotional cognitive processing in response to emotional stimulation patterns were explored by designing two experimental paradigms of an 8-minute open and closed eye resting task and an emotional face oddball task. Power spectrum and event-related potentials were extracted to explore the effect of tACS on brain rhythm modulation and attention modulation. It was found that the experimental group showed significantly enhanced alpha rhythm in the whole brain range after tACS, especially in the parieto-occipital lobe. The rate of misclassification of neutral emotions into negative emotions was significantly lower and the amplitude of P2 and P3 of event-related potentials were significantly higher when performing the emotional face task after tACS, while the control group did not have this phenomenon. These results suggest that tACS can modulate and enhance alpha rhythm activity by synchronizing alpha oscillations in the frontoparietal attention network, thereby improving subjects' negative emotion cognitive bias and enhancing their emotion processing by increasing early and late levels of emotional attention.

CUBIC-plus: An optimized method for rapid tissue clearing and decolorization.

Advanced CUBIC clearing method can clear diverse organs and even the entire body of a mouse to enable high-resolution 3D imaging. Advanced CUBIC reagent has often been used due to its low toxicity and easy preparation. However, Advanced CUBIC has a long experimental cycle, which reduces the efficiency of data acquisition. In this study, we first tracked the clarity changes of different organs cleared by Advanced CUBIC and identified the shortest time required for optimal transparency in individual organs. We then introduced ultrasound processing and developed a decolorization cocktail to optimize the clearing efficiency of the Advanced CUBIC method. With the optimized clearing CUBIC-Plus method, we achieved high resolution 3D imaging of mouse organs. Our CUBIC-Plus provides an efficient procedure to clear different organ for 3D imaging at high resolution.

A Slc25a46 Mouse Model Simulating Age-Associated Motor Deficit, Redox Imbalance, and Mitochondria Dysfunction.

The mitochondrial theory of aging postulates that accumulation of mtDNA mutations and mitochondrial dysfunction are responsible for producing aging phenotypes. To more comprehensively explore the complex relationship between aging and mitochondria dysfunction, we have developed a mouse model with Slc25a46 knockout, a nuclear gene described as encoding mitochondrial carriers, by CRISPR/Cas9 gene editing to mimic some typical aging phenotypes in human. Slc25a46-/- mice present segmental premature aging phenotypes characterized by shortened life span of no more than 2 months, obviously defective motor ability, gastrocnemius muscle atrophy, and imbalance of redox level in brain and liver. The underlying mechanism for multiple organ disorder may attribute to mitochondrial dysfunction, which is mainly manifested in the damaged mitochondrial structure (eg, vacuolar structure, irregular swelling, and disorganized cristae) and an age-associated decrease in respiratory chain enzyme (mainly complex I and IV) activity. In summary, our study suggests that the Slc25a46-/- mouse is a valid animal model for segmental aging-related pathologies studies based on mitochondrial theory, generating a new platform to both understand mechanisms between aging and mitochondria dysfunction as well as to design mitochondria-based therapeutic strategies to improve mitochondrial quality, and thereby the overall healthspan.