Composition of breast milk from mothers of premature and full-term infants and its influence in Z-Scores for infant physical growth.

BACKGROUND: Breast milk contains various crucial nutrients and biologically active substances and is ideal for newborns. This study aimed to analyze the composition of breast milk from mothers of premature and full-term infants and its influences on the growth of infants. METHODS: Infant-mother dyads examined at our Hospital (March 2016 to May 2017) were included. Milk was collected at 0-1 month, 2-3 months, and 5-6 months and analyzed using a MIRIS human milk analyzer. Z-scores of weight-for-length (WLZ), weight-for-age (WAZ), and length-for-age (LAZ) were calculated. RESULTS: This study included full-term (> 37 weeks of gestation, n = 177) and premature (< 37 weeks, n = 94) infant-mother dyads. The premature infants showed higher ΔWAZ, ΔLAZ, and ΔWLZ from infancy to toddlerhood for the physical growth speed, compared with term infants (P < 0.001). All proteins and true protein components of breast milk decreased with infants' age (P < 0.001). For premature and full-term infants, differences in ΔWAZ and ΔLAZ from birth to infancy and the difference in ΔLAZ, WAZ, and LAZ in toddlerhood were positively associated with non-protein nitrogen (NPN) (all P < 0.05), while the Z-score differences in ΔWLZ from birth to infancy were negatively associated with NPN (all P < 0.05). For premature babies, from birth to infancy stage, ΔWAZ was positively correlated with NPN and carbohydrates while negatively correlated with dry matter (all P < 0.05), and ΔLAZ correlated with NPN (ß = 0.428, P = 0.005). CONCLUSION: Breastfeeding helped premature infants compensatory growth when compared to term infants. Whileduring early infancy stage ΔWLZ gain was negatively associated with increased amounts of NPN in breast milk. This might mean although NPN increase the Z-scores of weight-for-age and length-for-age, with no rise in adipose tissue mass.

Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis.

Stroke can lead to severe nerve injury and debilitation, resulting in considerable social and economic burdens. Due to the high complexity of post-injury repair mechanisms, drugs approved for use in stroke are extremely scarce, and thus, the discovery of new antistroke drugs and targets is critical. Tryptophan hydroxylase 1 (TPH1) is involved in a variety of mental and neurobehavioral processes, but its effects on stroke have not yet been reported. Here, we used primary astrocyte culture, quantitative real-time PCR, double immunofluorescence assay, lentiviral infection, cell viability analysis, Western blotting, and other biochemical experiments to explore the protective mechanism of peptide OM-LV20, which previously exhibited neuroprotective effects in rats after ischemic stroke via a mechanism that may involve TPH1. First, we showed that TPH1 was expressed in rat astrocytes. Next, we determined that OM-LV20 impacted expression changes of TPH1 in CTX-TNA2 cells and exhibited a protective effect on the decrease in cell viability and catalase (CAT) levels induced by hydrogen peroxide. Importantly, we also found that TPH1 expression induced by OM-LV20 may be related to the level of change in the pituitary adenylate cyclase-activating peptide type 1 receptor (PAC1R) and to the JNK signaling pathways, thereby exerting a protective effect on astrocytes against oxidative stress. The protective effects of OM-LV20 likely occur via the 'PAC1R/JNK/TPH1' axis, thus highlighting TPH1 as a novel antistroke drug target.

A short peptide exerts neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis.

BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Peptide OM-LV20 promotes structural and functional recovery of spinal cord injury in rats.

At present, there are no satisfactory therapeutic drugs for the functional recovery of spinal cord injury (SCI). We previously identified a novel peptide (OM-LV20) that accelerated the regeneration of injured skin tissues of mice and exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats. Here, the intraperitoneal injection of OM-LV20 (1 µg/kg) markedly improved motor function recovery in the hind limbs of rats with traumatic SCI, and further enhanced spinal cord repair. Administration of OM-LV20 increased the number of surviving neuron bodies, as well as the expression levels of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). In the acute stage of SCI, OM-LV20 treatment also increased superoxide dismutase and glutathione content but decreased the levels of malonaldehyde and nitric oxide. Thus, OM-LV20 significantly promoted structural and functional recovery of SCI in adult rats by increasing neuronal survival and BDNF and TrkB expression, and thereby regulating the balance of oxidative stress. Based on our knowledge, this research is the first report on the effects of amphibian-derived peptide on the recovery of SCI and our results highlight the potential of peptide OM-LV20 administration in the acceleration of the recovery of SCI.

Scorpion venom peptide HsTx2 suppressed PTZ-induced seizures in mice via the circ_0001293/miR-8114/TGF-ß2 axis.

BACKGROUND: Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important. METHODS: BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription-quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-ß2 axis. RESULTS: The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-ß2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-ß2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo. CONCLUSIONS: HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-ß2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.

Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4+CD8+ T cells in ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is a heterogeneous disorder with complex pathogenesis. Therefore, in the present study, we aimed to assess genome-wide DNA methylation changes associated explicitly with the pathogenesis of UC. METHODS: DNA methylation changes were identified by comparing UC tissues with healthy controls (HCs) from the GEO databases. The candidate genes were obtained and verified in clinical samples. Moreover, the underlying molecular mechanism related to Zbtb7b in the pathogenesis of UC was explored using the dextran sodium sulfate (DSS)-induced colitis model. RESULTS: Bioinformatic analysis from GEO databases confirmed that Zbtb7b, known as Th-inducing POZ-Kruppel factor (ThPOK), was demethylated in UC tissues. Then, we demonstrated that Zbtb7b was in a hypo-methylation pattern through the DSS-induced colitis model (P = 0.0357), whereas the expression of Zbtb7b at the mRNA and protein levels was significantly up-regulated in the inflamed colonic tissues of UC patients (qRT-PCR, WB, IHC: P < 0.0001, P = 0.0079, P < 0.0001) and DSS-induced colitis model (qRT-PCR, WB, IHC: P < 0.0001, P = 0.0045, P = 0.0004). Moreover, the expression of Zbtb7b was positively associated with the degree of UC activity. Mechanically, over-expression of Zbtb7b might activate the maturation of CD4+T cells (FCM, IF: P = 0.0240, P = 0.0003) and repress the differentiation of double-positive CD4+CD8+T (DP CD4+CD8+T) cells (FCM, IF: P = 0.0247, P = 0.0118), contributing to the production of inflammatory cytokines, such as TNF-α (P = 0.0005, P = 0.0005), IL-17 (P = 0.0014, P = 0.0381), and IFN-γ (P = 0.0016, P = 0.0042), in the serum and colonic tissue of DSS-induced colitis model. CONCLUSIONS: Epigenetic DNA hypo-methylation of Zbtb7b activated the maturation of CD4+T cells and repressed the differentiation of DP CD4+CD8+ T cells, resulting in the production of inflammatory cytokines and colonic inflammation in UC. Therefore, Zbtb7b might be a diagnostic and therapeutic biomarker for UC, and hypo-methylation might affect the biological function of Zbtb7b.

Peptide OM-LV20 exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats.

Ischemia/reperfusion (I/R) is a common injury leading to ischemic stroke. At present, I/R treatment remains limited, highlighting the urgent need for the discovery and development of new protective drugs for brain injury. Here, we investigated the neuroprotective effects of short peptide OM-LV20 previously identified from amphibian against I/R rats. Results showed that intraperitoneal administration of OM-LV20 (20 ng/kg) significantly reduced infarct area formation, improved behavioral abnormalities, and protected cortical and hippocampal neurons against death caused by I/R. Moreover, the underlying molecular mechanism was involved with the regulation of the MAPK and BDNF/AKT signaling pathways, as well as the levels of cyclic adenosine monophosphate, pituitary adenylate cyclase-activating polypeptide receptor, and tryptophan hydroxylase 1. To the best of our knowledge, this research was the first report to describe the neuroprotective effects of an amphibian skin secretion-derived peptide in I/R rats and highlighted OM-LV20 as a promising drug candidate for the development of novel anti-stroke therapies.

The efficacy and safety of underwater endoscopic mucosal resection for ≥10-mm colorectal polyps: systematic review and meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is a promising strategy for nonpedunculated colorectal polyp removal. However, the efficacy and safety of the technique for the treatment of ≥ 10-mm colorectal polyps remain unclear. We aimed to comprehensively assess the efficacy and safety of UEMR for polyps sized 10-19 mm and ≥ 20 mm. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for relevant articles from January 2012 to November 2019. Primary outcomes were the rates of adverse events and residual polyps. Secondary outcomes were the complete resection, en bloc resection, and R0 resection rates. RESULTS: 18 articles including 1142 polyps from 1093 patients met our inclusion criteria. The overall adverse event and residual polyp rates were slightly lower for UEMR when removing colorectal polyps of 10-19 mm vs. ≥ 20 mm (3.5 % vs. 4.3 % and 1.2 % vs. 2.6 %, respectively). The UEMR-related complete resection rate was slightly higher for colorectal polyps of 10-19 mm vs. ≥ 20 mm (97.9 % vs. 92.0 %). However, the en bloc and R0 resection rates were dramatically higher for UEMR removal of polyps of 10-19 mm vs. ≥ 20 mm (83.4 % vs. 36.1 % and 73.0 % vs. 40.0 %, respectively). In addition, univariate meta-regression revealed that polyp size was an independent predictor for complete resection rate (P = 0.03) and en bloc resection (P = 0.01). CONCLUSIONS: UEMR was an effective and safe technique for the removal of ≥ 10-mm nonpedunculated colorectal polyps. However, UEMR exhibited low en bloc and R0 resection rates for the treatment of ≥ 20-mm polyps.

Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds.

Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence 'QNSYADLWCQFHYMC') from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-ß1 and TGF-ß3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis, and oral ulcers. Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.

The beneficial roles of poisonous skin secretions in survival strategies of the odorous frog Odorrana andersonii.

The evolution of predatory, anti-predatory, and defensive strategies regarding environmental adaptation in animals is of significant research interest. In particular, amphibians, who represent a transition between aquatic and terrestrial vertebrates, play an important role in animal evolution. The bioactive skin secretions of amphibians are of specific interest due to their involvement in the crucial physiological functions of amphibian skin. We previously isolated and identified several bioactive peptides, including those showing antioxidant, antimicrobial, and wound-healing properties, from the skin secretions of the odorous frog species Odorrana andersonii. Currently, however, the biological significance of skin secretions in O. andersonii survival remains unclear. Here, we studied the biological significance of skin glands and secretions in regard to environmental adaptations of O. andersonii. Our research found that O. andersonii may secrete and excrete bioactive secretions through many glands (peptides and proteins as the main components in glands) distributed in the skin. The skin secretions not only displayed toxicity but also showed antioxidant, antibacterial, and repair promoting activities, suggesting that they play a protective role in O. andersonii when facing environmental threats. These bioactive skin secretions appear to act as a chemical survival strategy in O. andersonii, allowing the species to gain advantages in survival behavior.

Factors associated with diagnostic accuracy, technical success and adverse events of endoscopic ultrasound-guided fine-needle biopsy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is used to diagnose lesions within or adjacent to the digestive tract. However, there is no report on the overall diagnostic accuracy, technical success, and adverse events of FNB. The aims of this study were to conduct a systematic review and meta-analysis to comprehensively assess the diagnostic accuracy, technical success, and adverse events of FNB. METHODS: Pubmed, Embase, and Cochrane Library databases were searched for relevant articles published in English from January 1998 to May 2019 (No. CRD42019141647). Primary outcomes were EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate. RESULTS: A total of 51 articles including 5330 patients met our criteria. The overall EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate was 90.82% [95% confidence interval (CI) 88.69-92.76%], 99.71% [95% CI 99.35-99.93%], and 0.59% [95% CI 0.29-1.0%], respectively. Biopsy with 22G needle could increase the diagnostic accuracy rate and technical success rate to 92.17% [95% CI 89.32-94.61%] and 99.88% [95% CI 99.64-99.99%], respectively, and decrease the adverse event to 0.37% [95% CI 0.08-0.87%]. Moreover, it showed that 22G needle was an independent factor associated with a higher diagnostic accuracy rate and technical success rate and a lower adverse event rate (P = 0.04, P < 0.001, and P = 0.04, respectively) by univariate and multivariate meta-regression analyses. CONCLUSION: Endoscopic ultrasound-guided fine-needle biopsy is a feasible and safe procedure for lesions within or adjacent to the digestive tract. Biopsy using 22G needle could increase the diagnostic accuracy rate and technical success rate and decrease adverse event rate during the FNB procedure.

Endocut Versus Conventional Blended Electrosurgical Current for Endoscopic Biliary Sphincterotomy: A Meta-Analysis of Complications.

BACKGROUND AND AIMS: Endoscopic biliary sphincterotomy (EST) is commonly performed during therapeutic endoscopic retrograde cholangiopancreatography (ERCP), but is an independent risk factor for post-ERCP pancreatitis, bleeding and duodenal perforation. These are partly ascribed to the electrosurgical current mode used for EST, and currently the optimal current model for EST remains controversial. In this study, we aimed to compare the rate of complications undergoing EST using the Endocut versus the blended current. METHODS: A systematic search of databases was performed for relevant published and prospective studies including randomized clinical trials (RCTs) to compare Endocut with blended current modes for EST. Data were collected from inception until 1 July 2018, using post-ERCP pancreatitis, bleeding and perforation as primary outcomes. RESULTS: Three RCTs including a total of 594 patients met the inclusion criteria. Our meta-analysis results showed the rate of post-ERCP pancreatitis, primarily mild to moderate pancreatitis, was no different between Endocut versus blended current modes [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.25-1.52, P = 0.29]. However, the risk of endoscopically bleeding events, primarily mild bleeding, was lower in studies using Endocut versus blended current (RR 0.54, 95% CI 0.31-0.95, P = 0.03). Notably, none of the patients experienced perforation in these three trials. CONCLUSIONS: The rate of post-ERCP pancreatitis was not significantly different when using the Endocut versus blended current during EST. Nevertheless, compared with the blended current, Endocut reduced the incidence of endoscopically evident bleeding; however, the available data were insufficient to assess the perforation risk.

Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.

Long non-coding RNAs (lncRNAs) are important regulators of many cellular processes, and their aberrant expression and/or function is associated with many different diseases, including cancer. However, the identification of functional lncRNAs in gastric cancer is still a challenge. In this study, we describe a novel functional lncRNA, linc00483, that is upregulated and associated with tumorigenesis, tumour size, metastasis and poor prognosis in gastric cancer. In our study, linc00483 promoted gastric cancer cell proliferation, invasiveness and metastasis in vitro and in vivo. Mechanistically, upregulated expression of linc00483 in gastric cancer acts as a sponge to absorb endogenous tumour suppressor miR-30a-3p. Furthermore, it restores SPAG9 expression, which is negatively regulated by miR-30a-3p, and actives MAPK signaling pathway in gastric cancer cells. Thus, linc00483 is an oncogenic lncRNA in gastric cancer and targeting linc00483 or its pathway can potentially be useful in development of targeted therapies for patients with gastric cancer. Our results show that linc00483 is an important regulator in carcinogenesis and may be a useful biomarker to predict prognosis of gastric cancer patients. We believe our findings are novel and will be of interest to scientists working in many areas related to biomarkers in cancer.

Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models.

Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Identification and evaluation of a risk model predicting the prognosis of breast cancer based on characteristic signatures.

Background: Breast cancer (BC) is one of the most common fatal cancers in women. Identifying new biomarkers is thus of great significance for the diagnosis and prognosis of BC. Methods: In this study, 1,030 BC cases from The Cancer Genome Atlas (TCGA) were obtained for differential expression analysis and Short Time-series Expression Miner (STEM) analysis to identify characteristic BC development genes, which were further divided into upregulated and downregulated genes. Two predictive prognosis models were both defined by Least Absolute Shrinkage and Selection Operator (LASSO). Survival analysis and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic and prognostic capabilities of the two gene set model scores, respectively. Results: Our findings from this study suggested that both the unfavorable (BC1) and favorable (BC2) gene sets are reliable biomarkers for the diagnosis and prognosis of BC, although the BC1 model presents better diagnostic and prognostic value. Associations between the models and M2 macrophages and sensitivity to Bortezomib were also found, indicating that unfavorable BC genes are significantly involved in the tumor immune microenvironment. Conclusions: We successfully established one predictive prognosis model (BC1) based on characteristic gene sets of BC to diagnose and predict the survival time of BC patients using a cluster of 12 differentially expressed genes (DEGs).

Selective integration of diverse taste inputs within a single taste modality.

A fundamental question in sensory processing is how different channels of sensory input are processed to regulate behavior. Different input channels may converge onto common downstream pathways to drive the same behaviors, or they may activate separate pathways to regulate distinct behaviors. We investigated this question in the Drosophila bitter taste system, which contains diverse bitter-sensing cells residing in different taste organs. First, we optogenetically activated subsets of bitter neurons within each organ. These subsets elicited broad and highly overlapping behavioral effects, suggesting that they converge onto common downstream pathways, but we also observed behavioral differences that argue for biased convergence. Consistent with these results, transsynaptic tracing revealed that bitter neurons in different organs connect to overlapping downstream pathways with biased connectivity. We investigated taste processing in one type of downstream bitter neuron that projects to the higher brain. These neurons integrate input from multiple organs and regulate specific taste-related behaviors. We then traced downstream circuits, providing the first glimpse into taste processing in the higher brain. Together, these results reveal that different bitter inputs are selectively integrated early in the circuit, enabling the pooling of information, while the circuit then diverges into multiple pathways that may have different roles.

Mesenchymal Stem Cell-derived Exosomes: Novel Therapeutic Approach for Inflammatory Bowel Diseases.

As double membrane-encapsulated nanovesicles (30-150 nm), exosomes (Exos) shuttle between different cells to mediate intercellular communication and transport active cargoes of paracrine factors. The anti-inflammatory and immunomodulatory activities of mesenchymal stem cell (MSC)-derived Exos (MSC-Exos) provide a rationale for novel cell-free therapies for inflammatory bowel disease (IBD). Growing evidence has shown that MSC-Exos can be a potential candidate for treating IBD. In the present review, we summarized the most critical advances in the properties of MSC-Exos, provided the research progress of MSC-Exos in treating IBD, and discussed the molecular mechanisms underlying these effects. Collectively, MSC-Exos had great potential for cell-free therapy in IBD. However, further studies are required to understand the full dimensions of the complex Exo system and how to optimize its effects.

Emerging role of bacterial outer membrane vesicle in gastrointestinal tract.

Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract's health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.

Nanomaterials for mRNA-based therapeutics: Challenges and opportunities.

Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA-based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano-drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano-design materials exert functions for specific mRNA applications, provide new perception for next-generation nanomaterials, and thus revolution of mRNA technology.