Data-balanced transformer for accelerated ionizable lipid nanoparticles screening in mRNA delivery.

Despite the widespread use of ionizable lipid nanoparticles (LNPs) in clinical applications for messenger RNA (mRNA) delivery, the mRNA drug delivery system faces an efficient challenge in the screening of LNPs. Traditional screening methods often require a substantial amount of experimental time and incur high research and development costs. To accelerate the early development stage of LNPs, we propose TransLNP, a transformer-based transfection prediction model designed to aid in the selection of LNPs for mRNA drug delivery systems. TransLNP uses two types of molecular information to perceive the relationship between structure and transfection efficiency: coarse-grained atomic sequence information and fine-grained atomic spatial relationship information. Due to the scarcity of existing LNPs experimental data, we find that pretraining the molecular model is crucial for better understanding the task of predicting LNPs properties, which is achieved through reconstructing atomic 3D coordinates and masking atom predictions. In addition, the issue of data imbalance is particularly prominent in the real-world exploration of LNPs. We introduce the BalMol block to solve this problem by smoothing the distribution of labels and molecular features. Our approach outperforms state-of-the-art works in transfection property prediction under both random and scaffold data splitting. Additionally, we establish a relationship between molecular structural similarity and transfection differences, selecting 4267 pairs of molecular transfection cliffs, which are pairs of molecules that exhibit high structural similarity but significant differences in transfection efficiency, thereby revealing the primary source of prediction errors. The code, model and data are made publicly available at https://github.com/wklix/TransLNP.

Genetic events associated with venetoclax resistance in CLL identified by whole-exome sequencing of patient samples.

Although BCL2 mutations are reported as later occurring events leading to venetoclax resistance, many other mechanisms of progression have been reported though remain poorly understood. Here, we analyze longitudinal tumor samples from 11 patients with disease progression while receiving venetoclax to characterize the clonal evolution of resistance. All patients tested showed increased in vitro resistance to venetoclax at the posttreatment time point. We found the previously described acquired BCL2-G101V mutation in only 4 of 11 patients, with 2 patients showing a very low variant allele fraction (0.03%-4.68%). Whole-exome sequencing revealed acquired loss(8p) in 4 of 11 patients, of which 2 patients also had gain (1q21.2-21.3) in the same cells affecting the MCL1 gene. In vitro experiments showed that CLL cells from the 4 patients with loss(8p) were more resistant to venetoclax than cells from those without it, with the cells from 2 patients also carrying gain (1q21.2-21.3) showing increased sensitivity to MCL1 inhibition. Progression samples with gain (1q21.2-21.3) were more susceptible to the combination of MCL1 inhibitor and venetoclax. Differential gene expression analysis comparing bulk RNA sequencing data from pretreatment and progression time points of all patients showed upregulation of proliferation, B-cell receptor (BCR), and NF-κB gene sets including MAPK genes. Cells from progression time points demonstrated upregulation of surface immunoglobulin M and higher pERK levels compared with those from the preprogression time point, suggesting an upregulation of BCR signaling that activates the MAPK pathway. Overall, our data suggest several mechanisms of acquired resistance to venetoclax in CLL that could pave the way for rationally designed combination treatments for patients with venetoclax-resistant CLL.

Comprehensive evaluation of molecule property prediction with ChatGPT.

The versatility of ChatGPT in performing a diverse range of tasks has elicited considerable interest on its potential applications within professional fields. Taking drug discovery as a testbed, this paper provides a comprehensive evaluation of ChatGPT's ability on molecule property prediction. The study focuses on three aspects: 1) Effects of different prompt settings, where we investigate the impact of varying prompts on the prediction outcomes of ChatGPT; 2) Comprehensive evaluation on molecule property prediction, where we conduct a comprehensive evaluation on 53 ADMET-related endpoints; 3) Analysis of ChatGPT's potential and limitations, where we make comparisons with models tailored for molecule property prediction, thus gaining a more accurate understanding of ChatGPT's capabilities and limitations in this area. Through comprehensive evaluation, we find that 1) With appropriate prompt settings, ChatGPT can attain satisfactory prediction outcomes that are competitive with specialized models designed for those tasks. 2) Prompt settings significantly affect ChatGPT's performance. Among all prompt settings, the strategy of selecting examples in few-shot has the greatest impact on results. Scaffold sampling greatly outperforms random sampling. 3) The capacity of ChatGPT to accomplish high-precision predictions is significantly influenced by the quality of examples provided, which may constrain its practical applicability in real-world scenarios. This work highlights ChatGPT's potential and limitations on molecule property prediction, which we hope can inspire future design and evaluation of Large Language Models within scientific domains.

Chiral Au-Pd Alloy Nanorods with Tunable Optical Chirality and Catalytically Active Surfaces.

Integrating the plasmonic chirality with excellent catalytic activities in plasmonic hybrid nanostructures provides a promising strategy to realize the chiral nanocatalysis toward many chemical reactions. However, the controllable synthesis of catalytically active chiral plasmonic nanoparticles with tailored geometries and compositions remains a significant challenge. Here it is demonstrated that chiral Au-Pd alloy nanorods with tunable optical chirality and catalytically active surfaces can be achieved by a seed-mediated coreduction growth method. Through manipulating the chiral inducers, Au nanorods selectively transform into two different intrinsically chiral Au-Pd alloy nanorods with distinct geometric chirality and tunable optical chirality. By further adjusting several key synthetic parameters, the optical chirality, composition, and geometry of the chiral Au-Pd nanorods are fine-tailored. More importantly, the chiral Au-Pd alloy nanorods exhibit appealing chiral catalytic activities as well as polarization-dependent plasmon-enhanced nanozyme catalytic activity, which has great potential for chiral nanocatalysis and plasmon-induced chiral photochemistry.

Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome.

Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) is typically chemoresistant, with a poor prognosis. We hypothesized that the oral Bcl-2 inhibitor venetoclax could sensitize RS to chemoimmunotherapy and improve outcomes. We conducted a single-arm, investigator-sponsored, phase 2 trial of venetoclax plus dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-EPOCH) to determine the rate of complete response (CR). Patients received R-EPOCH for 1 cycle, then after count recovery, accelerated daily venetoclax ramp-up to 400 mg, then VR-EPOCH for up to 5 more 21-day cycles. Responders received venetoclax maintenance or cellular therapy off-study. Twenty-six patients were treated, and 13 of 26 (50%) achieved CR, with 11 achieving undetectable bone marrow minimal residual disease for CLL. Three additional patients achieved partial response (overall response rate, 62%). Median progression-free survival was 10.1 months, and median overall survival was 19.6 months. Hematologic toxicity included grade ≥3 neutropenia (65%) and thrombocytopenia (50%), with febrile neutropenia in 38%. No patients experienced tumor lysis syndrome with daily venetoclax ramp-up. VR-EPOCH is active in RS, with deeper, more durable responses than historical regimens. Toxicities from intensive chemoimmunotherapy and venetoclax were observed. Our data suggest that studies comparing venetoclax with chemoimmunotherapy to chemoimmunotherapy alone are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03054896.

Genome-wide association study and genomic selection of spike-related traits in bread wheat.

KEY MESSAGE: Identification of 337 stable MTAs for wheat spike-related traits improved model accuracy, and favorable alleles of MTA259 and MTA64 increased grain weight and yield per plant. Wheat (Triticum aestivum L.) is one of the three primary global, staple crops. Improving spike-related traits in wheat is crucial for optimizing spike and plant morphology, ultimately leading to increased grain yield. Here, we performed a genome-wide association study using a dataset of 24,889 high-quality unique single-nucleotide polymorphisms (SNPs) and phenotypic data from 314 wheat accessions across eight diverse environments. In total, 337 stable and significant marker-trait associations (MTAs) related to spike-related traits were identified. MTA259 and MTA64 were consistently detected in seven and six environments, respectively. The presence of favorable alleles associated with MTA259 and MTA64 significantly reduced wheat spike exsertion length and spike length, while enhancing thousand kernel weight and yield per plant. Combined gene expression and network analyses identified TraesCS6D03G0692300 and TraesCS6D03G0692700 as candidate genes for MTA259 and TraesCS2D03G0111700 and TraesCS2D03G0112500 for MTA64. The identified MTAs significantly improved the prediction accuracy of each model compared with using all the SNPs, and the random forest model was optimal for genome selection. Additionally, the eight stable and major MTAs, including MTA259, MTA64, MTA66, MTA94, MTA110, MTA165, MTA180, and MTA164, were converted into cost-effective and efficient detection markers. This study provided valuable genetic resources and reliable molecular markers for wheat breeding programs.

Extracellular vesicle therapy for obesity-induced NAFLD: a comprehensive review of current evidence.

Non-alcoholic fatty liver disease (NAFLD) as a chronic disease especially in Western countries, is still a tough question in the clinical therapy. With the rising prevalence of various chronic diseases, liver transplantation is expected to be the most common therapy after the next 10 years. However, there is still no approved drug for NAFLD, and targeted therapy for NAFLD is urgent. Exosomes as a kind of extracellular vesicle are cell-derived nanovesicles, which play an essential role in intercellular communication. Due to complex cell-cell interactions in the liver, exosomes as therapeutic drugs or drug delivery vesicles may be involved in physiological or pathological processes in NAFLD. Compared with other nanomaterials, exosomes as a cell-free therapy, are not dependent on cell number limitation, which means can be administered safely in high doses. Apart from this, exosomes with the advantages of being low-toxic, high stability, and low-immunological are chosen for targeted therapy for many diseases. In this review, firstly we introduced the extracellular vesicles, including the biogenesis, composition, isolation and characterization, and fundamental function of extracellular vesicles. And then we discussed the modification of extracellular vesicles, cargo packing, and artificial exosomes. Finally, the extracellular vesicles for the therapies of NAFLD are summarized. Moreover, we highlight therapeutic approaches using exosomes in the clinical treatment of NAFLD, which provide valuable insights into targeting NAFLD in the clinical setting.

Fungal vaccines and adjuvants: a tool to reveal the interaction between host and fungi.

Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants.

Physical impediment to sodium houttuyfonate conversely reinforces ß-glucan exposure stimulated innate immune response to Candida albicans.

Candida albicans is a dimorphic opportunistic pathogen in immunocompromised individuals. We have previously demonstrated that sodium houttuyfonate (SH), a derivative of medicinal herb Houttuynia cordata Thunb, was effective for antifungal purposes. However, the physical impediment of SH by C. albicans ß-glucan may weaken the antifungal activity of SH. In this study, the interactions of SH with cell wall (CW), extracellular matrix (EM), CW ß-glucan, and a commercial ß-glucan zymosan A (ZY) were inspected by XTT assay and total plate count in a standard reference C. albicans SC5314 as well as two clinical fluconazole-resistant strains Z4935 and Z5172. After treatment with SH, the content and exposure of CW ß-glucan, chitin, and mannan were detected, the fungal clearance by phagocytosis of RAW264.7 and THP-1 was examined, and the gene expressions and levels of cytokines TNF-ɑ and IL-10 were also monitored. The results showed that SH could be physically impeded by ß-glucan in CW, EM, and ZY. This impediment subsequently triggered the exposure of CW ß-glucan and chitin with mannan masked in a time-dependent manner. SH-induced ß-glucan exposure could significantly enhance the phagocytosis and inhibit the growth of C. albicans. Meanwhile, the SH-pretreated fungal cells could greatly stimulate the cytokine gene expressions and levels of TNF-ɑ and IL-10 in the macrophages. In sum, the strategy that the instant physical impediment of C. albicans CW to SH, which can induce the exposure of CW ß-glucan may be universal for C. albicans in response to physical deterrent by antifungal drugs.

Melatonin restores hepatic lipid metabolic homeostasis disrupted by blue light at night in high-fat diet-fed mice.

Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV-ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV-ERBs. In addition, different effects of light wavelengths at night on liver REV-ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV-ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short-wavelength-dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.

PbBeB2O5: A High-Performance Ultraviolet Nonlinear-Optical Crystal with Functional [BeB2O8]8- Group.

High-performance nonlinear-optical (NLO) crystals need to simultaneously meet multiple basic and conflicting performance requirements. Here, by using a partial chemical substitution strategy, the first noncentrosymmetric (NCS) PbBeB2O5 crystal with a BeB2O8 group was synthesized, exhibiting a two-dimensional [BeB2O5]∞ layer constructed by interconnecting BeB2O8 groups and bridged PbO4 with an active lone pair. The crystal shows a promising UV NLO functional feature, including a strong SHG effect of 3.5 × KDP (KH2PO4), large birefringence realizing phase matchability in the whole transparency region from 246 to 2500 nm, a short UV absorption edge of 246 nm, and single-crystal easy growth. Remarkably, theoretical studies reveal that the BeB2O8 group has high nonlinear activity, which could stimulate the discovery of a series of excellent NLO beryllium borates.

Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy.

Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.

Hesperetin protects hippocampal neurons from the neurotoxicity of Aflatoxin B1 in mice.

Aflatoxin B1 (AFB1) is a major food and feed pollutant that endangers public health. Previous studies have shown that exposure to AFB1 causes neurotoxicity in the body. However, the mechanism of neurotoxicity caused by AFB1 is not well understood, and finding a workable and practical method to safeguard animals from AFB1 toxicity is essential. This study confirmed that AFB1 caused endoplasmic reticulum stress (ER stress) and apoptosis in hippocampal neurons using C57BL/6 J mice and HT22 cells as models. In vitro experiments showed that the aryl hydrocarbon receptor (AHR) plays a significant role in the cytotoxicity of AFB1. Finally, we assessed how hesperetin protecting against the neurotoxicity caused by AFB1. Our findings demonstrated that AFB1 increased the levels of BAX and Cleaved-Caspase3 proteins, while decreasing the levels of BCL2 protein in the CA1 and CA3 regions of the hippocampus. The AFB1 increased the expression of AHR and activated nuclear translocation. It also elevated the expression levels of Chop, GRP78, p-IRE1/ Xbp1s, and p-PERK/p-EIF2a. Importantly, we also discovered for the first time that blocking AHR in HT22 cells dramatically reduced the level of ER stress and apoptosis caused by AFB1. In vivo and in vitro studies, supplementation of hesperetin effectively reversed AFB1-induced cytotoxicity. We have demonstrated that hesperetin effectively restored the imbalance in the GSH/GST system in HT22 cells treated with AFB1. Furthermore, we observed that elevated GSH levels facilitated the formation of AFB1-GSH complexes, which enhanced the excretion of AFB1. Therefore, hesperetin improves ER stress-induced apoptosis by reducing AFB1 activation of AHR.

Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A.

Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin's protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.

5-HT attenuates chronic stress-induced cognitive impairment in mice through intestinal flora disruption.

BACKGROUND: The microbiota-gut-brain axis plays an important role in the development of depression. The aim of this study was to investigate the effects of 5-HT on cognitive function, learning and memory induced by chronic unforeseeable mild stress stimulation (CUMS) in female mice. CUMS mice and TPH2 KO mice were used in the study. Lactococcus lactis E001-B-8 fungus powder was orally administered to mice with CUMS. METHODS: We used the open field test, Morris water maze, tail suspension test and sucrose preference test to examine learning-related behaviours. In addition, AB-PAS staining, immunofluorescence, ELISA, qPCR, Western blotting and microbial sequencing were employed to address our hypotheses. RESULTS: The effect of CUMS was more obvious in female mice than in male mice. Compared with female CUMS mice, extracellular serotonin levels in TPH2 KO CUMS mice were significantly reduced, and cognitive dysfunction was aggravated. Increased hippocampal autophagy levels, decreased neurotransmitter levels, reduced oxidative stress damage, increased neuroinflammatory responses and disrupted gut flora were observed. Moreover, L. lactis E001-B-8 significantly improved the cognitive behaviour of mice. CONCLUSIONS: These results strongly suggest that L. lactis E001-B-8 but not FLX can alleviate rodent depressive and anxiety-like behaviours in response to CUMS, which is associated with the improvement of 5-HT metabolism and modulation of the gut microbiome composition.

Melatonin improves skin barrier damage caused by sleep restriction through gut microbiota.

It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite.

Cerium-Encapsulated SbIII-SeIV-Templating Polyoxotungstate for Electrochemically Sensing Human Multidrug Resistance Gene Segment.

A tower-like SbIII-SeIV-templating polyoxotungstate [H2N(CH3)2]12Na7H3[Ce0.5/Na0.5(H2O)5]2[SbSe2W21O75]2·50H2O (1) was synthesized, whose skeleton is assembled from two prolonged lacunary Dawson [SbSe2W21O75]13- units and two [Ce0.5/Na0.5(H2O)5]2+ linkers. The uncommon [SbSe2W21O75]13- unit can be viewed as a combination of one [SeW6O21]2- group grafted onto a trivacant Dawson [SbSeW15O54]11- subunit. The conductive composite 1-Au@rGO containing 1, gold nanoparticles, and reduced graphene oxide (rGO) was conveniently prepared, using which the 1-Au@rGO-based electrochemical genosensor was constructed for detecting human multidrug resistance gene segment. This work enriches structural types of dual-heteroatom-inserted polyoxometalates and promotes the application of polyoxometalates in genosensors.

Effect of traditional Chinese medicine combined group psychotherapy on psychological distress management and gut micro-biome regulation for colorectal cancer survivors: a single-arm phase I clinical trial.

OBJECTIVE: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine (TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal (CRC) survivors. METHODS: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan Hospital and Beijing Cancer Hospital in China. Inclusion criteria included stage I-III CRC survivors after radical surgery with age between 18 and 75. The intervention was a 6-week online TCM combined group psychotherapy intervention including 90-min communication, TCM lifestyle coaching, self-acupressure guidance, and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire (QLQ-C30). Fecal samples before and after intervention were collected for 16Sr RNA analysis. RESULTS: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years' old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4 (37.9±10.5) and week 6 (31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2 (28.3±8.8, p<0.001) and week 6 (25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4 (p=0.038) and 16.3±5.8 at week 6 (p=0.008). Although changes of QLQ-C30 were not statistically prominent, symptom burden of insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter, and Gordonibacter were all significantly elevated after intervention. CONCLUSIONS: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors' psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.

Eucommia ulmoides polysaccharide modified nano-selenium effectively alleviated DSS-induced colitis through enhancing intestinal mucosal barrier function and antioxidant capacity.

Ulcerative colitis (UC) is currently the most common inflammatory bowel disease (IBD). Due to its diverse and complex causes, there is no cure at present, and researchers are constantly exploring new therapies. In recent years, nano-selenium particle(SeNP) has attracted wide attention due to excellent biological activities. Therefore, in this study, for the first time, we used a natural polysaccharide, Eucommia ulmoides polysaccharide (EUP), modified SeNP to get EUP-SeNP with a size of about 170 nm, and its effect on 3% dextran sulphate sodium (DSS) induced colitis was explored. Our results showed that colon intestinal histology, intestinal mucosal barrier, inflammatory cytokines and intestinal microbiome composition were changed after EUP-SeNP treatment in colitis mice. Specifically, it was also shown that oral treatment of EUP-SeNP could relieve the degree of DSS-induced colitis in mice by restoring weight loss, reducing disease activity index (DAI), enhancing colon antioxidant capacity and regulating intestinal microbiome composition. In addition, we verified the mechanism in intestinal epithelial cell lines, showing that EUP-SeNP inhibited LPS-induced activation of the TRL-4/NF-κB signaling pathway in intestinal epithelial cell lines. To some extend, our study provides therapeutic reference for the treatment of IBD.

Insulin ameliorates dim blue light at night-induced apoptosis in hippocampal neurons via the IR/IRS1/AKT/GSK3ß/ß-catenin signaling pathway.

In recent years, the damaging effects of night light pollution, one of the environmental pollutions, on memory has been attracting attention. However, the underlying molecular mechanisms by which light at night, especially blue light at night, impairs memory remains unclear. Here, a total of 42 C57BL6/J mice that exposed to no light at night, dim white light at night (dLAN-WL), or dim blue light at night (dLAN-BL) for 28 days. Behavioral data indicated that exposure to dLAN-BL resulted in severe recognition memory impairment, as evidenced by the reduced recognition index and discrimination index in the novel object recognition test. At the same time, we observed a decrease in plasma insulin levels. Consistent with these changes, we also observed that dLAN-BL reduced the number of neurons in the CA1, CA3 and DG regions of the hippocampus, up-regulated the mRNA expression levels of Bax, down-regulated the mRNA expression levels of Bcl-2, Bcl-xl and the protein expression level of pIRS1, pAKT, pGSK3ß, ß-catenin in the hippocampus. In vitro experiments, we found that insulin (10 nM) inhibited apoptosis and up-regulated the protein expression levels of pAKT, pGSK3ß, ß-catenin of HT22 cells induced by H2O2 (200 µM). However, these changes disappeared when the insulin receptors (IR) in HT22 cells were silenced. Taken together, our findings suggested that the impairment of memory in mice induced by dLAN-BL was mediated by insulin via the IR/IRS1/AKT/GSK3ß/ß-catenin pathway. DATA AVAILABILITY: All data generated or analyzed during this study are included in this published article.