Efficacy and safety of acupuncture in the treatment of stroke complicated with sleep apnea syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: stroke patients often have a combination of sleep apnea syndrome, which is an important and modifiable risk factor for stroke prognosis. Acupuncture is one of the measures for sleep apnea syndrome, and it is also widely used in stroke. However, we are concerned that its efficacy and safety in the treatment of stroke with sleep apnea syndrome are not yet clear. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses schema and was registered with INPLASY (registration number: INPLASY202250113). The following 8 databases were searched: PubMed, Cochrane Library (CENTRAL), Embase, Web of Science, China National Knowledge Infrastructure, Chongqing VIP Information, WanFang Data, and China Biomedical Literature Database limited from the establishment of each database to May 4, 2022. Subject headings, free words, and keywords were used for retrieval. Relevant literature was supplemented by consulting other resources. We assessed the risk of bias in the included studies using the Cochrane risk of bias tool. RevMan 5.4 software (The Cochrane Collaboration, 2020) was used to perform the meta-analysis. RESULTS: Six records were included, including a total of 513 participants: 256 in the experimental group and 257 in the control group. The results showed that the total effective rate (relative risk = 1.23, 95% confidence interval (CI): 1.13, 1.34, P < .00001), apnea-hypopnea index (mean difference (MD) = -8.39, 95% CI: -9.19, -7.59, P < .00001), Epworth Sleepiness Scale score (MD = -1.59, 95% CI: -2.66, -0.52, P = .004), minimal oxygen saturation (MD = 4.99, 95% CI: 3.5, 6.47, P < .00001), longest duration of apnea (MD = -7.47, 95% CI: -8.97, -5.97, P < .00001), longest duration of apnea (MD = -6.48, 95% CI: -8.60, -4.35, P < .00001), and S100ß levels (standard mean difference = -1.52, 95% CI: -1.87, -1.18, P < .00001) were better in the experimental group than in the control group. Simultaneously, the effect of reducing the neuron-specific enolase level in the experimental group was comparable to that in the control group (MD = -3.40, 95% CI: -9.08, 2.29, P = .24). CONCLUSIONS: Acupuncture can improve the clinical symptoms and related laboratory indicators for sleep apnea syndrome in patients with stroke. More high-quality trials remain urgently needed.

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation (TEAS) As An Analgesic Intervention for Labor Pain: A Network Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Epidural analgesia (EA) is the most widely used intervention for the reduction of labor pain; however, it is contra-indicated for patients with spinal deformity or allergy to anesthetics and may be refused by parturients. As a noninvasive and nonnarcotic analgesic intervention, transcutaneous electrical acupoint stimulation (TEAS) has gained increasing attention in recent years. Therefore, we performed a network meta-analysis to compare the efficacy and safety of TEAS and EA as measured by visual analog scale score, the failure rate of natural delivery, adverse events, and Apgar scores. METHODS: Relevant randomized controlled trials (RCTs) from four electronic databases (PubMed, EMBASE, Web of Science, and Cochrane CENTRAL) and clinical trials.gov were searched from inception until September 4, 2022. A random effects model was used during analysis, and outcomes were evaluated as standard mean difference (SMD), odds ratio (OR), and 95% confidence intervals (CrI) using STATA (version SE15.0), R (version 3.6.1), and ADDIS (version 1.16.8) software. RESULTS: Ten RCTs comprising 1214 parturients were identified by screening. Six RCTs compared TEAS and controls, three compared EA and controls, and one compared TEAS and EA. No heterogeneity was found within the four outcomes. There was no significant difference in any outcomes between interventions or control treatments in terms of SMD, OR, and CrI. Combined with the highest surface under the cumulative ranking curve score, TEAS demonstrated possible better effects in the aspects of analgesic efficacy and safety under certain circumstances. CONCLUSIONS: TEAS may be a potential alternative for parturients as a simple, noninvasive, and non-pharmacological intervention compared with EA in terms of analgesic efficacy and safety for mothers and neonates.

Effects of sodium tanshinone IIA sulfonate injection on inflammatory factors and vascular endothelial function in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized clinical trials.

Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) therapy may experience further damage to the vascular endothelium, leading to increased inflammatory response and in-stent thrombosis. In many clinical studies, sodium tanshinone IIA sulfonate injection (STS) has been found to reduce inflammatory factors and enhance vascular endothelial function in patients with ACS while improving the prognosis of PCI. However, to date, there has been no systematic review assessing the effectiveness and safety of STS on inflammatory factors and vascular endothelial function. Purpose: The aim of this study is to systematically review the effects of STS on inflammatory factors and endothelial function in patients with ACS treated with PCI. Methods: Until October 2022, eight literature databases and two clinical trial registries were searched for randomized controlled trials (RCTs) investigating STS treatment for ACS patients undergoing PCI. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool 2.0. Meta-analysis was performed using RevMan 5.4 software. Results: Seventeen trials met the eligibility criteria, including 1,802 ACS patients undergoing PCI. The meta-analysis showed that STS significantly reduced high-sensitivity C-reactive protein (hs-CRP) levels (mean difference [MD = -2.35, 95% CI (-3.84, -0.86), p = 0.002], tumor necrosis factor-alpha (TNF-α) levels (standard mean difference [SMD = -3.29, 95%CI (-5.15, -1.42), p = 0,006], matrix metalloproteinase-9 (MMP-9) levels [MD = -16.24, 95%CI (-17.24, -15.24), p < 0.00001], and lipid peroxidation (LPO) levels [MD = -2.32, 95%CI (-2.70, -1.93), p < 0.00001], and increased superoxide dismutase (SOD) levels [SMD = 1.46, 95%CI (0.43, 2.49), p = 0,006] in patients with ACS. In addition, STS significantly decreased the incidence of major adverse cardiovascular events (relative risk = 0.54, 95%CI [0.44, 0.66], p < 0.00001). The quality of evidence for the outcomes was assessed to be very low to medium. Conclusion: STS can safely and effectively reduce the levels of hs-CRP, TNF-α, MMP-9, and LPO and increase the level of SOD in patients with ACS treated with PCI. It can also reduce the incidence of adverse cardiovascular events. However, these findings require careful consideration due to the small number of included studies, high risk of bias, and low to moderate evidence. In the future, more large-scale and high-quality RCTs will be needed as evidence in clinical practice.

Identification of Potential MicroRNA-MRNA Regulatory Relationship Pairs in Irritable Bowel Syndrome with Diarrhea.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common gastrointestinal disease worldwide, with diarrhea-predominant irritable bowel syndrome (IBS-D) being the prevalent subtype. However, its pathogenesis remains unclear. Research has increasingly focused on identifying genetic factors in the mechanisms underlying IBS. OBJECTIVE: We aimed to explore key gene nodes and potential microRNA-mRNA regulatory pairs of IBS-D using bioinformatics methods. METHODS: We downloaded the GSE36701 microarray dataset from the Gene Expression Omnibus database and obtained 1358 differentially expressed mRNAs by analyzing mRNA profiles using the GEO2R analysis tool. Based on our previous study, we used TargetScan, miTarBase, and miRDB to predict the downstream genes of three known microRNAs (hsa-let-7b-5p, hsa-miR-19b-3p, and hsamiR- 20a-5p), and the microRNA-mRNA regulatory network was visualized using Cytoscape. RESULTS: A total of 795 downstream target genes were found in TargetScan, miRTarBase, and miRDB databases, and 50 candidate genes were obtained. The Metascape and STRING databases were used to perform enrichment analysis and construct a protein-protein interaction network of candidate genes. Finally, we constructed a network of 3 microRNAs and 50 candidate mRNAs, among which 28 negative relation ship pairs and 5 key axes (hsa-miR-20a-5p/VEGFA, hsa-let-7b- 5p/MSN, hsa-let-7b-5p /PPP1R16B, hsa-19b-3p/ITGA2, and hsa-19b-3p/PIK3R3) were identified. CONCLUSION: We report five novel microRNA-mRNA regulatory axes in IBS-D pathogenesis and speculated that PIK3R3, negatively regulated by hsa-miR-19b-3p, may regulate NF-κB production through the PI3K/Akt pathway, which accounts for the occurrence of clinical symptoms in IBS-D patients. Our findings may offer key biomarkers for IBS-D diagnosis and treatment.

[Characteristics of Bone Marrow Cell Morphology and Immunophenotype in Patients with NHL Leukemia and Evaluation of NHL Bone Marrow Invasion].

OBJECTIVE: To observe the evaluation value of characteristics of bone marrow cell morphology and immunophenotype in patients with non-Hodgkin lymphoma (NHL) leukemia on the bone marrow invasion of NHL. METHODS: The clinical data of 104 patients with NHL treated in the hospital from March 2016 to March 2021 were retrospectively analyzed, the characteristics of bone marrow smear morphology were recorded, and the analysis of bone marrow immunophenotype was performed, the evaluation value of bone marrow cell morphology and immunophenotype on NHL bone marrow invasion was analyzed. RESULTS: One hundred and four patients with NHL leukemia were found to have increased lymphoma cells by examination of bone marrow cell morphology, including 57 cases of B-cell type, 39 cases of T-cell type and 8 cases of NK/T cell type. The characteristics of bone marrow cell morphology were as follows: the cell body was large, irregular or round like in shape, the cytoplasm was much and mostly stained blue, a few cells could see a few granules, the nucleus was round or round like, some were twisted, the chromatin was thick and nucleolus was different, of which the T-cell type lymphoma cells had strong heteromorphism and more obvious nucleolus. B-cell type mainly expressed CD19, HLA-DR and CD20, and the positive rate was ≥70%. T-cell type mainly expressed CD7, HLA-DR and CD38, and the positive rate was ≥40%. NK/T cell types mainly expressed CD56 and CD161, and the positive rates was ≥50%. Compared the proportion of lymphoma cells between bone marrow smear and immunophenotype examination, there was no statistical significant difference (P>0.05). CONCLUSION: The characteristics of bone marrow cell morphology and immunophenotype have certain application value in the evaluation of bone marrow invasion in patients with NHL leukemia, both can complement each other and provide a feasible mean for the effective evaluation of bone marrow invasion in patients with NHL leukemia.

Identification of circRNA-miRNA-mRNA Regulatory Network and Crucial Signaling Pathway Axis Involved in Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases (CHD) worldwide; however, its pathogenesis remains unclear. Recent studies have shown that circular RNAs (circRNAs) act as "sponges" for microRNAs (miRNAs) to compete for endogenous RNA (ceRNA) and play important roles in regulating gene transcription and biological processes. However, the mechanism of ceRNA in TOF remains unclear. To explore the crucial regulatory connections and pathways of TOF, we obtained the human TOF gene, miRNA, and circRNA expression profiling datasets from the Gene Expression Omnibus (GEO) database. After data pretreatment, differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified between the TOF and healthy groups, and a global triple ceRNA regulatory network, including circRNAs, miRNAs, and mRNAs based on the integrated data, was constructed. A functional enrichment analysis was performed on the Metascape website to explore the biological functions of the selected genes. Then, we constructed a protein-protein interaction (PPI) network and identified seven hub genes using the cytoHubba and MCODE plug-ins in the Cytoscape software, including BCL2L11, PIK3R1, SOCS3, OSMR, STAT3, RUNX3, and IL6R. Additionally, a circRNA-miRNA-hub gene subnetwork was established, and its enrichment analysis results indicated that the extrinsic apoptotic signaling pathway, JAK-STAT signaling pathway and PI3K-Akt signaling pathway may be involved in the pathogenesis of TOF. We further identified the hsa_circ_000601/hsa-miR-148a/BCL2L11 axis as a crucial signaling pathway axis from the subnetwork. This study provides a novel regulatory network for the pathogenesis of TOF, revealing the possible molecular mechanisms and crucial regulatory pathways that may provide new strategies for candidate diagnostic biomarkers or potential therapeutic targets for TOF.

Ethnic Specificity of Species and Strain Composition of Lactobacillus Populations From Mother-Infant Pairs, Uncovered by Multilocus Sequence Typing.

The maternal gut is thought to be the principal source of potential probiotic bacteria in the infant gut during the lactation stage. It is not clear whether facultative symbiont lactobacilli strictly follow vertical transmission from mother to infant and display the ethnic specificity in terms of species and strain composition in mother-infant cohorts. In the present study, a total of 16 former Lactobacillus species (365 strains) and 11 species (280 strains) were retrieved from 31 healthy mother-infant pairs of two ethnic groups, which have never intermarried, respectively. The result showed that the composition and number of Lactobacillus species between the two ethnic groups varied. Among 106 Lacticaseibacillus paracasei strains isolated, 64 representative strains were classified into 27 sequence types (ST) by means of multilocus sequence typing (MLST), of which 20 STs derived from 33 Uighur strains and 7 STs from 31 Li strains, and no homologous recombination event of genes was detected between strains of different ethnic groups. A go-EBURST analysis revealed that except for a few mother-infant pairs in which more than one STs were detected, L. paracasei isolates from the same mother-infant pair were found to be monophyletic in most cases, confirming vertical transfer of Lactobacillus at the strain level. More notably, L. paracasei isolates from the same ethnic group were more likely than strains from another to be incorporated into a specific phylogenetic clade or clonal complex (CC) with similar metabolic profile of glycan, supporting the hypothesis of ethnic specificity to a large degree. Our study provides evidence for the development of personalized probiotic tailored to very homogenous localized populations from the perspective of maternal and child health.

Gelling properties of silver carp surimi incorporated with konjac glucomannan: Effects of deacetylation degree.

Effects of konjac glucomannan (KGM) with different deacetylation degrees on silver carp surimi gel properties were studied. As deacetylation degree increased, viscosity, solubility, and water absorption capability of KGM decreased gradually while particle size increased. The gel strength of surimi gel increased with the KGM deacetylation degree up to 50.72% and then significantly decreased. The maximum gel strength was 3.26 times higher than that of surimi gel with native KGM. The relaxation time of immobilized water decreased from 108.22 to 104.70 ms and then increased up to 110.92 ms with the deacetylation degree, while the proportion of the immobilized water increased from 92.74 to 98.59% and then decreased to 97.46%. Water distribution became less uniform as the deacetylation degree exceeded 50.72%. Surimi gel with KGM of a higher deacetylation degree formed a denser microstructure along with a higher dimensional fraction value. However, the microstructure was disrupted and the dimensional fraction value decreased as the deacetylation degree exceeded 50.72%. Chemical interactions including hydrogen bonds, hydrophobic interactions, and cross-linking extent increased with the KGM deacetylation degree up to 50.72% and then gradually decreased. The results suggest that KGM with a deacetylation degree of 50.72% is the most suitable for surimi products.

Association and Occurrence of Bifidobacterial Phylotypes Between Breast Milk and Fecal Microbiomes in Mother-Infant Dyads During the First 2 Years of Life.

Breast milk acts as an intermediary for the transfer of functionally important commensal bacteria from mother to infant, especially for Bifidobacterium that can colonize the infant gut. However, the vast majority of rRNA amplicon-based studies reported the conspicuous intercohort and interindividual variation for the prevalence of Bifidobacterium in breast milk. In order to elucidate whether Bifidobacterium phylotypes persistently co-occured at the species or strain level in mother-breast milk-infant triads, we analyzed collectively the next-generation sequencing (NGS) datasets of bacterial 16S rRNA gene and the Bifidobacterium-specific groEL gene from maternal feces, breast milk, and infant feces in a small yet very homogeneous cohort of 25 healthy Uyghur mother-infant pairs (lactation for 7-720 days) in Kashgar, Xinjiang, China. Overall, 16S rRNA gene analysis showed that microbiome in the newborn gut was closer to that of breast milk in the first 4 months of lactation, and subsequently showed an obvious trend of adulthood at 6-12 months. Based on the BLAST accurate taxonomic result of the representative sequences of all ASVs (amplicon sequencing variants), only three sets of ASVs could be clearly assigned into Bifidobacterium species, whereas the remaining eight sets of ASVs corresponded to four indefinite Bifidobacterium species group. By contrast, the groEL gene dataset was partitioned into 376 ASVs, at least belonging to 13 well-known Bifidobacterium species or subspecies, of which 15 ASVs, annotated to seven well-known Bifidobacterium species or subspecies, showed triadic synchronism in most 23 mother-infant pairs tested. However, several other rare bifidobacterial phylotypes, which were frequently encountered in animals, were found to display no correspondence of the presence between the three ecosystems of mother-infant pairs. Our test results were obviously to support the hypothesis that breast milk acts as an intermediary for the transfer of probiotic commensal bacteria from mother to infant, especially for endosymbiotic Bifidobacterium that can colonize the infant gut. Some oxygen-insensitive exogenous Bifidobacterium phylotypes with a cosmopolitan lifestyle may be indirectly transferred to breast milk and the infant's intestinal tract through environmental contamination. Thus, the groEL gene proved to be a very effective target for the depth resolution of Bifidobacterium community by high-throughput sequencing technologies.

A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world, and there remains an urgent need to develop long-lasting therapies to treat CRC and prevent recurrence in patients. Oncolytic virus therapy (OVT) has demonstrated remarkable efficacy in a number of different cancer models. Here, we report a novel vaccinia virus (VV)-based OVT for treatment of CRC. The novel VV, based on the recently reported novel VVLΔTKΔN1L virus, was armed with the pleiotropic cytokine interleukin-21 (IL-21) to enhance anti-tumor immune responses stimulated after viral infection of tumor cells. Compared with an unarmed virus, VVLΔTKΔN1L-mIL-21 had a superior anti-tumor efficacy in murine CMT93 subcutaneous CRC models in vivo, mediated mainly by CD8+ T cells. Treatment resulted in development of long-term immunity against CMT93 tumor cells, as evidenced by prevention of disease recurrence. These results demonstrate that VVLΔTKΔN1L-mIL-21 is a promising therapeutic agent for treatment of CRC.

Chaperone-mediated autophagy affects tumor cell proliferation and cisplatin resistance in esophageal squamous cell carcinoma.

BACKGROUND: Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosomal membrane associated protein 2a (LAMP2a) is the lysosomal membrane receptor of CMA and influences CMA activity. Although it has been suggested that higher expression of LAMP2a is associated with more advanced tumor node metastasis (TNM) stages and shorter survival time in patients with esophageal squamous cell carcinoma (ESCC), the underlying mechanism has not been known yet. METHODS: In this study, we modulated the activity of CMA through LAMP2a or small molecular compounds in human ESCC cells to investigate its role in ESCC. RESULTS: We found that down-regulating the activity of CMA could inhibit the proliferation and colony formation of ESCC cells as well as increase their sensitivity to cisplatin. CONCLUSIONS: Our results promote better understanding of how CMA affects human ESCC and provide a new therapeutic target against ESCC through down-regulating LAMP2a.

Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime.

Lung cancer is one of the most commonly diagnosed cancer and despite therapeutic advances, mortality remains high. The long period of clinical latency associated with lung cancer provides an ideal window of opportunity to administer vaccines to at-risk individuals that can prevent tumor progression and initiate long-term anti-tumor immune surveillance. Here we describe a personalized vaccination regime that could be applied for both therapeutic and prophylactic prevention of lung cancer, based on the derivation of lung cancer cells from induced pluripotent stem cells. Stem cells from healthy mice were modified to express Cre-dependent KRASG12D and Trp53R172H prior to differentiation to lung progenitor cells. Subsequent viral delivery of Cre caused activation of exogenous driver mutations, resulting in transformation and development of lung cancer cells. iPSC-derived lung cancer cells were highly antigenically related to lung cancer cells induced in LSL-KRASG12D/+; Trp53R172H/+ transgenic mice and were antigenically unrelated to original pluripotent stem cells or pancreatic cancer cells derived using the same technological platform. For vaccination, induced lung cancer cells were infected with oncolytic Adenovirus or Vaccinia virus, to act as vaccine adjuvants, prior to delivery of vaccines sequentially to a murine inducible transgenic model of lung cancer. Application of this Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime primed tumor-specific T cell responses that significantly prolonged survival in both subcutaneous post-vaccine challenge models and induced transgenic models of lung cancer, demonstrating that stem cell-derived prophylactic vaccines may be a feasible intervention for treatment or prevention of lung cancer development in at-risk individuals.

Physicochemical changes of MTGase cross-linked surimi gels subjected to liquid nitrogen spray freezing.

Physicochemical properties of microbial transglutaminase (MTGase) cross-linked surimi gels subjected to liquid nitrogen (LN) spray freezing with different temperatures and cross-linking degrees were investigated. Gels with lower LN spray temperature (-90 °C) were found taking less time in cooling down themselves to maximum-ice-crystal generating temperature. Microstructure images showed the pores of gels became smaller and the structure gradually became denser, as freezing temperature decreased and cross-linking degree increased. It also revealed T22 relaxation time of gels decreased significantly with surimi gels cross-linking degree increasing, indicating the binding ability of gels to moisture was enhanced accordingly. Meanwhile, the proton density weighted image brightness declined along with the LN spray temperature decreasing, and the image brightness showed a decreasing trend from outside to inside, indicating that water migrated and permeated easier from the inside of the gel network to the outside undergone higher LN temperature and lower cross-linking degree. Besides, the L⁎ and W values of LN groups decreased along with LN spray temperature and cross-linking degree increasing. Moreover, -90 °C LN group with 46.70% cross-linking degree presented the highest breaking force which ascribed to their synergistic efforts in maintaining a stable and dense structure of gels via controlling ice crystals and cross-linkages' generation.

Studies on the bioactivities and molecular mechanism of antioxidant peptides by 3D-QSAR, in vitro evaluation and molecular dynamic simulations.

Two novel effective antioxidative tripeptides GWY and QWY were designed based on 3D-QSAR models. Their activities were confirmed by an improved TEAC assay. The experimental results showed that GWY and QWY possessed good antioxidant activity, equaling 3.32 mM TE and 2.97 mM TE respectively. This indicated that 3D-QSAR models possessed significant predictive capacity for drug design. In addition, molecular docking and molecular dynamics simulation were applied to reveal the potential molecular mechanism of antioxidant peptides. The result showed that GWY and QWY could enhance the stability of Keap1 by interacting with the key residues Arg415, Arg483, Arg380 and Ser555 in the active sites. Interestingly, the key residues were exactly the binding site of Nrf2 in the active pocket of Keap1. Thus, GWY and QWY could compete with Nrf2 for binding to Keap1. This demonstrated that the new tripeptides might have the ability to activate the signaling pathway Keap1-Nrf2-ARE and improve the antioxidant defense system of the body as well.

The Composition and Concordance of Lactobacillus Populations of Infant Gut and the Corresponding Breast-Milk and Maternal Gut.

The maternal gut is the principal source of commensal bacteria in the infant gut during the lactation stage, where breast milk acts as an intermediary for the transfer of potential probiotic bacteria consortia, including Lactobacillus. This study aimed to characterize the bacterial communities in human milk, maternal, and infant feces in a small yet very homogeneous cohort of 25 healthy mother-infant pairs in northwestern China (n = 25, infant age from 7 days to 2 years), with special emphasis on the cooccurrence and vertical transfer of Lactobacillus phylotypes at the species or strain level in mother-breast milk-infant triads. Accurate sequencing analysis revealed that among 73 Lactobacillus zero-radius operational classification units (ZOTUs) identified, 58 belonging to 18 recognized species or species groups were distributed in all three types of samples. Lactobacillus ruminis, L. mucosae and L. gasseri-johnsonii as true residents were the most represented in all three ecosystems, whereas the content of Lactobacillus phylotypes commonly developed as probiotics was not dominant. While the numbers of Lactobacillus species in breast milk and infant feces were greater than that in maternal feces, principal coordinates analysis (PCoA) based on beta diversity, coupled with the frequency of isolates determined by culture methods, showed that the Lactobacillus community in the infant gut was more similar to that in the maternal gut than to that in breast milk, suggesting that the gut is niche selective for Lactobacillus populations. In addition, identical strains of L. ruminis, L. paracasei, L. mucosae and L. salivarius were isolated from multiple mother-infant pairs, supporting the hypothesis that vertical transfer of bacteria via breastfeeding contributes to the initial establishment of the microbiota in the developing infant intestine.

A Virus-Infected, Reprogrammed Somatic Cell-Derived Tumor Cell (VIReST) Vaccination Regime Can Prevent Initiation and Progression of Pancreatic Cancer.

PURPOSE: Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses. EXPERIMENTAL DESIGN: We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRas G12D and p53 R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development. RESULTS: Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual's stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic. CONCLUSIONS: These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.

Habitat-specificity and diversity of culturable cold-adapted yeasts of a cold-based glacier in the Tianshan Mountains, northwestern China.

Asian cold-based glacier yeasts with respect to their abundance, distribution, and taxonomy, in contrast to other continental cryosphere areas, have been little investigated. The present study reports the diversity and phylogeny of culturable cold-adapted yeasts in six cold habitats of the Glacier No.1 in the Tianshan Mountains (northwestern China). Of the total 591 yeast isolates, 401 were identified as basidiomycetous yeasts represented by 41 species of 15 genera, while 190 ascomycetous yeast isolates were assigned to the 8 species of 7 genera. The most prevalent species was Candida akabanensis with a 19.8% frequency of occurrence, followed by Vishniacozyma victoriae (16.4%) and Diutina rugosa (9.98%), of which V. victoriae was the only yeast species common to all six glacial habitats. Variability on the component and abundance of yeast taxa among glacial habitats primarily displayed in four dominant yeast genera, namely Candida, Vishniacozyma, Filobasidium, and Naganishia. However, network analysis illustrated that most of 32 rare yeast populations were habitat-specific, implying that the low-abundance yeast population was more easily influenced by the local habitat conditions (species sorting). Based on indicator species analyses, the subglacial habitat was characterized by psychrotolerant and/or psychrophilic yeast taxa.

Small G Rac1 is involved in replication cycle of dengue serotype 2 virus in EAhy926 cells via the regulation of actin cytoskeleton.

Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the pathogenesis of severe dengue remains unclear. In this study, we showed that the Rac1-microfilament signal pathway was involved in the process of DENV serotype 2 (DENV2) infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Rac1 activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Rac1 promoted DENV2 entry but inhibited viral assembly, maturation and release. Our findings demonstrated that Rac1 plays an important role in the DENV2 life cycle by regulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.

Characterization of konjac glucomannan-ethyl cellulose film formation via microscopy.

Konjac glucomannan-ethyl cellulose (KGM-EC, 7:3, w/w) blended film shows good mechanical and moisture resistance properties. To better understand the basis for the KGM-EC film formation, optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) were used to observe the formation of the film from emulsion. Optical microscopy images showed that EC oil droplets were homogeneously dispersed in KGM water phase without obviously coalescence throughout the entire drying process. SEM images showed the surface and cross-sectional structures of samples maintained continuous and homogeneous appearance from the emulsion to dried film. AFM images indicated that KGM molecules entangled EC molecules in the emulsion. Interactions between KGM and EC improved the stability of KGM-EC emulsion, and contributed to uniformed structures of film formation. Based on these output information, a schematic model was built to elucidate KGM-EC film-forming process.