Dynamic hydrogel-metal-organic framework system promotes bone regeneration in periodontitis through controlled drug delivery.

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment's impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel's synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.

Rhizosphere environmental factors regulated the cadmium adsorption by vermicompost: Influence of pH and low-molecular-weight organic acids.

Vermicompost is a promising amendment for immobilization of cadmium (Cd) in soils; however, its effectiveness can be influenced by rhizosphere environment conditions, such as pH and the presence of low-molecular-weight organic acids (LMWOAs). In this study, a batch experiment was conducted to examine the characteristics of Cd adsorption by vermicompost at different pH (pH = 3, 5, and 7) and after the addition of different LMWOAs (oxalic acid; citric acid; malic acid). Furthermore, a series of morphology and structural analyses were conducted to elucidate the mechanisms of observed effects. The results showed that the adsorption capacity of vermicompost for Cd increased as pH increased, and chemisorption dominated the adsorption process. Changes in pH altered adsorption performance by affecting the -OH groups of alcohol/phenol and the -CH2 groups of aliphatics. Further, the addition of oxalic acid promoted Cd adsorption, and the effect was concentration dependent. Modifying the verimicompost surface with more adsorption sites might be the main reason. Conversely, citric acid and malic acid showed the ability to inhibit Cd adsorption by vermicompost. Citric acid caused a blocking effect by covering flocculent substances on the vermicompost surface while reducing surface adsorption sites by dissolving mineral components such as iron oxides. However, the action of malic acid did not appear to be related to changes in morphology or the structure of vermicompost. Overall, the results of this study partially explain the limited effectiveness of Cd immobilization within the rhizosphere by vermicompost, and provide theoretical support for regulating rhizosphere environments to improve the effectiveness of vermicompost immobilization of Cd.

A novel hexa-segmented dsRNA mycovirus confers hypovirulence in the phytopathogenic fungus Diaporthe pseudophoenicicola.

A novel hexa-segmented double-stranded RNA (dsRNA) mycovirus was isolated and characterized from the filamentous phytopathogenic fungus Diaporthe pseudophoenicicola and was named Diaporthe pseudophoenicicola chrysovirus 1 (DpCV1). The full-length cDNAs of dsRNA1-6 were 3335, 3030, 3039, 2980, 963, and 780 bp, respectively. Sequence analysis indicated the presence of nine open reading frames (ORFs) in the DpCV1 genome. ORF1 in dsRNA1 putatively encoded the RNA-dependent RNA polymerase (RdRp) and ORF3 in dsRNA2 encoded a capsid protein (CP). The seven remaining ORFs, ORF2 in dsRNA2, ORF4 in dsRNA3, ORF6, seven in dsRNA4, ORF8 in dsRNA5, and ORF9 in dsRNA6, encoded proteins with unknown functions. Phylogenetic analysis revealed that DpCV1 is closely related to members of the cluster I group within the family Chrysoviridae but formed a separate clade. Importantly, all the six segments of DpCV1 were cured successfully through single spore isolation to obtain the isogenic virus-free strains. DpCV1 can confer hypovirulence to the fungal host of Diaporthe pseudophoenicicola. Compared with the virus-free strain, WC02 harbouring the DpCV1 is more sensitive to fungicide prochloraz. Furthermore, the cell wall of DpCV1 infected strain was loose and enlarged. This is the first report of a hexa-segmented tentative chrysovirus in D. pseudophoenicicola.

Epstein-Barr virus infection-associated cholangiocarcinoma: a report of one case and the review of literature.

The clinical data of a patient with Epstein-barr virus (EBV) associated with cholangiocarcinoma was reported in this paper: a case of a 36-year-old female presented with abdominal pain and systemic skin yellowing combined with skin itching. Laboratory studies showed increase in alanine aminotransferase 242 U/L, aspartate aminotransferase 404 U/L, r-glutamyltransferase 1516 U/L, total bilirubin 308.2 µmol/L and CA199 (101.0 U/ml). AFP (4.5 ng/ml) was normal. CT revealed multiple space-occupying lesions in the liver. PET-CT revealed liver malignant tumor and lymph node metastasis. Liver puncture pathology revealed infiltrative growth of significant heterocyst nests in the liver tissue, which was morphologically consistent with malignant tumors, considering poorly differentiated carcinoma. Pathology suggestion: combining liver puncture with morphology, immunohistochemistry, and EBV in situ hybridization results, it was consistent with EB virus-associated poorly differentiated carcinoma, therefore, consider EBV infection-associated poorly differentiated cholangiocarcinoma (CCA) (LELC morphology). The patient underwent liver transplantation in Hangzhou Shulan Hospital on June 8, 2021 successfully. After surgery, the patient orally took tacrolimus for anti-rejection, entecavir for antiviral therapy, gemcitabine 1.2 g + cis-platinum 30 mg for chemotherapy. After following up for more than 5 months post liver transplantation, the condition of the patient deteriorated. The patient subsequently died. Based on the case of our patient and the review of existing literature, when the patient's serum CA199 increased, AFP did not change significantly, and there was no previous history of hepatitis B. CT revealed a low-density mass in the liver, ring enhancement in the arterial phase, and heterogeneous enhancement of the tumor in the delayed phase. Ring enhancement of the liver lesion mass was observed on MRI. Consider the might possibility of hepatic CCA. When patients showed recurrent tonsillitis at an early age, EBV virus infection should be vigilant and oropharyngeal tissue should persist, diagnosis of EBV-associated liver cancer should be considered. In particular, EBV infection-related liver cancer is relatively rare, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

Development of a Novel Primer-TaqMan Probe Set for Diagnosis and Quantification of Meloidogyne enterolobii in Soil Using qPCR and Droplet Digital PCR Assays.

Early detection of pathogens before the planting season is valuable to forecast disease occurrence. Therefore, rapid and reliable diagnostic approaches are urgently needed, especially for one of the most aggressive root knot nematodes, Meloidogyne enterolobii. In this study, we developed a novel primer-TaqMan probe set aimed at M. enterolobii. The primer-probe set was successfully applied in the identification and quantification of M. enterolobii via qPCR technology. It was also suitable for improved PCR technology, known as ddPCR analyses, and this work presents the first application of this technology for plant parasitic nematodes. Compared with qPCR, ddPCR exhibited better performance with regard to analytical sensitivity, which can provide a more accurate detection of M. enterolobii concealed in field soil. In addition, we generated standard curves to calculate the number of eggs in soil using the qPCR and ddPCR platforms. Hopefully, the results herein will be helpful for forecasting disease severity of M. enterolobii infection and adopting effective management strategies.

Gremlin1 Delivered by Mesenchymal Stromal Cells Promoted Epithelial-Mesenchymal Transition in Human Esophageal Squamous Cell Carcinoma.

Backgroud/Aims: Mesenchymal stromal cells (MSCs) are a major component of the tumor microenvironment (TME). Several studies focusing on tumor-derived MSCs have demonstrated that they exhibit a strong ability to promote the tumor epithelial-mesenchymal transition (EMT). However, the factors mediating these effects are poorly understood. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry assays were used to detect the expression of Gremlin1 (GREM1) in human esophageal squamous cell carcinoma (ESCC) tissues. ShRNA silencing, flow cytometry, cell counting kit (CCK8) assay, invasion assay, western blot were used to detect the effect of GREM1 in ECa109, TE-1 cell lines and xenograft tumor models. RESULTS: In the current study, we found that the GREM1 was overexpressed in human ESCC tissues. The conditioned medium from mesenchymal stromal cells (MSCs-CM) enhanced the malignancy of xenograft esophageal tumors in vivo, as well as the cell proliferation, viability and invasion of the esophageal carcinoma cell lines ECa109 and TE-1 in vitro. Furthermore, the shRNA silencing of GREM1 in MSCs (shGREM1-MSCs) reversed the increased malignancy of the esophageal tumor in vivo, while the conditioned medium from shGREM1-MSCs (shGREM1-MSCs-CM) affected the cell cycle and cell invasion in vitro. These processes were accompanied by the EMT in the ECa109 and TE-1 cell lines with an alteration in the expression levels of mesenchymal and epithelial markers. Furthermore, the TGF-ß/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling pathway participated in the shGREM1-MSCs-CM-induced anti-tumor effect on enhanced esophageal malignancy induced by MSCs-CM treatment. CONCLUSIONS: Taken together, our study suggested that GREM1 delivered by MSCs promoted EMT in ESCC in vitro and in vivo, which is partly through TGF-ß/BMP signaling pathway. The results provide experimental evidence to a potential therapeutic target in the treatment of esophageal cancer.

YY1 promotes IL-6 expression in LPS-stimulated BV2 microglial cells by interacting with p65 to promote transcriptional activation of IL-6.

Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.

Nanotubular topography enhances the bioactivity of titanium implants.

Surface modification on titanium implants plays an important role in promoting mesenchymal stem cell (MSC) response to enhance osseointegration persistently. In this study, nano-scale TiO2 nanotube topography (TNT), micro-scale sand blasted-acid etched topography (SLA), and hybrid sand blasted-acid etched/nanotube topography (SLA/TNT) were fabricated on the surfaces of titanium implants. Although the initial cell adherence at 60 min among TNT, SLA and TNT/SLA was not different, SLA and SLA/TNT presented to be rougher and suppressed the proliferation of MSC. TNT showed hydrophilic surface and balanced promotion of cellular functions. After being implanted in rabbit femur models, TNT displayed the best osteogenesis inducing ability as well as strong bonding strength to the substrate. These results indicate that nano-scale TNT provides favorable surface topography for improving the clinical performance of endosseous implants compared with micro and hybrid micro/nano surfaces, suggesting a promising and reliable surface modification strategy of titanium implants for clinical application.

Tcf7l2 localization of putative stem/progenitor cells in mouse conjunctiva.

Conjunctival integrity and preservation is indispensable for vision. The self-renewing capacity of conjunctival cells controls conjunctival homeostasis and regeneration; however, the source of conjunctival self-renewal and the underlying mechanism is currently unclear. Here, we characterize the biochemical phenotype and proliferative potential of conjunctival epithelial cells in adult mouse by detecting proliferation-related signatures and conducting clonal analysis. Further, we show that transcription factor 7-like 2 (T-cell-specific transcription factor 4), a DNA binding protein expressed in multiple types of adult stem cells, is highly correlated with proliferative signatures in basal conjunctival epithelia. Clonal studies demonstrated that Transcription factor 7-like 2 (Tcf7l2) was coexpressed with p63α and proliferating cell nuclear antigen (PCNA) in propagative colonies. Furthermore, Tcf7l2 was actively transcribed concurrently with conjunctival epithelial proliferation in vitro. Collectively, we suggest that Tcf7l2 may be involved in maintenance of stem/progenitor cells properties of conjunctival epithelial stem/progenitor cells, and with the fornix as the optimal site to isolate highly proliferative conjunctival epithelial cells in adult mice.

Normative anthropometric analysis and aesthetic indication of the ocular region for young Chinese adults.

PURPOSE: The ocular region is of prime importance for the facial aesthetic outlook. Various anthropometric analyses for the periocular region have developed to ensure a pleasing postoperative appearance. However, little information exists for Chinese young adults. In this study, authors not only analyzed the periocular anthropometric characteristics, but, more importantly, searched out the most meaningful aesthetic indicators of the population. METHODS: The cross-sectional study was executed using two-dimensional photogrammetry acquired from 162 Chinese young adults (79 males, 83 females) between 20-30 years old. Anthropometric parameters including palpebral fissure length and height, intercanthal and outercanthal width, crease height, angle of endocanthion and exocanthion, axis of palpebral fissure, palpebral fissure index, canthal index, and angular index were acquired from standardized photographs. Then, 134 volunteers (20-30 years old) gave each photograph a score within 1-5 points to evaluate their ocular aesthetic attractiveness. The correlation between anthropometric parameters and aesthetic assessment was analyzed. RESULTS: A statistical difference between genders was found for palpebral fissure length and height, outercanthal width, angle of exocanthion, palpebral fissure index and canthal index (p < 0.05), with no statistical difference found for crease height between genders. Moreover, the palpebral fissure index, canthal index, crease height, and angle of exocanthion were significantly associated with aesthetic assessment. CONCLUSIONS: The normative anthropometric parameters are fundamental to interpret the morphology of eyes and to design plastic surgery for young Chinese adults. The parameters of palpebral fissure index, canthal index, crease height, and angle of exocanthion are strong indicators of aesthetic assessment.

Polar localization of a symbiosis-specific phosphate transporter is mediated by a transient reorientation of secretion.

The arbuscular mycorrhizal (AM) symbiosis, formed by land plants and AM fungi, evolved an estimated 400 million years ago and has been maintained in angiosperms, gymnosperms, pteridophytes, and some bryophytes as a strategy for enhancing phosphate acquisition. During AM symbiosis, the AM fungus colonizes the root cortical cells where it forms branched hyphae called arbuscules that function in nutrient exchange with the plant. Each arbuscule is enveloped in a plant membrane, the periarbuscular membrane, that contains a unique set of proteins including phosphate transporters such as Medicago truncatula MtPT4 [Javot et al., (2007) Proc Natl Acad Sci USA 104:1720-1725], which are essential for symbiotic phosphate transport. The periarbuscular membrane is physically continuous with the plasma membrane of the cortical cell, but MtPT4 and other periarbuscular membrane-resident proteins are located only in the domain around the arbuscule branches. Establishing the distinct protein composition of the periarbuscular membrane is critical for AM symbiosis, but currently the mechanism by which this composition is achieved is unknown. Here we investigate the targeting of MtPT4 to the periarbuscular membrane. By expressing MtPT4 and other plasma membrane proteins from promoters active at different phases of the symbiosis, we show that polar targeting of MtPT4 is mediated by precise temporal expression coupled with a transient reorientation of secretion and alterations in the protein cargo entering the secretory system of the colonized root cell. In addition, analysis of phosphate transporter mutants implicates the trans-Golgi network in phosphate transporter secretion.

A novel bi-layered asymmetric membrane incorporating demineralized dentin matrix accelerates tissue healing and bone regeneration in a rat skull defect model.

Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

The Arabidopsis chloroplast division protein DYNAMIN-RELATED PROTEIN5B also mediates peroxisome division.

Peroxisomes are highly dynamic organelles involved in various metabolic pathways. The division of peroxisomes is regulated by factors such as the PEROXIN11 (PEX11) proteins that promote peroxisome elongation and the dynamin-related proteins (DRPs) and FISSION1 (FIS1) proteins that function together to mediate organelle fission. In Arabidopsis thaliana, DRP3A/DRP3B and FIS1A (BIGYIN)/FIS1B are two pairs of homologous proteins known to function in both peroxisomal and mitochondrial division. Here, we report that DRP5B, a DRP distantly related to the DRP3s and originally identified as a chloroplast division protein, also contributes to peroxisome division. DRP5B localizes to both peroxisomes and chloroplasts. Mutations in the DRP5B gene lead to peroxisome division defects and compromised peroxisome functions. Using coimmunoprecipitation and bimolecular fluorescence complementation assays, we further demonstrate that DRP5B can interact or form a complex with itself and with DRP3A, DRP3B, FIS1A, and most of the Arabidopsis PEX11 isoforms. Our data suggest that, in contrast with DRP3A and DRP3B, whose orthologs exist across plant, fungal, and animal kingdoms, DRP5B is a plant/algal invention to facilitate the division of their organelles (i.e., chloroplasts and peroxisomes). In addition, our results support the notion that proteins involved in the early (elongation) and late (fission) stages of peroxisome division may act cooperatively.

Renal venous malformation misdiagnosed as carcinoma: A report of one case and the review of literature.

The present study reports the clinical data of a patient with renal venous malformation misdiagnosed as carcinoma. CT revealed hematocele in the left renal pelvis and ureter. CTU: the left renal pelvis and calyces showed a slightly high density shadow, a size of about 2.6 cm*1.5 cm, and mild-to-moderate enhancement was found at the edge of the lesion. Enhanced MR showed that irregular mass abnormal signal was observed in the lower calyx of the left kidney and the lesions were cast, with short T1 and slightly long T2 signals. The secondary bleeding or mucus of low-grade malignant tumor became suspicious. The patient underwent cystoscopy and left ureteroscopy under general anesthesia on December 3, 2021. Bloody urine can be seen on the left side, and multiple blood clots in the left renal pelvis can be detected. After washing, dark red bloody necrotic substances can be seen. Pathology suggests that renal venous malformation, accompanied by bleeding and thrombosis, is located in the renal medulla, involving the renal calyx, rupture and bleeding of the renal calyx, and obvious local bleeding of surrounding renal tissue. Follow-up for more than 1 year showed that the patient's condition was stable. When patients have renal colic with hematuria, enhanced CT suggests that renal mass is mild-to-moderate continuous enhancement, enhanced MRI suggests short T1 and long T2, considering that the mass may be accompanied by bleeding, and ureteroscopy suggests that dark red bloody necrotic substances should be considered in the diagnosis of renal venous malformation.

STTA: enhanced text classification via selective test-time augmentation.

Test-time augmentation (TTA) is a well-established technique that involves aggregating transformed examples of test inputs during the inference stage. The goal is to enhance model performance and reduce the uncertainty of predictions. Despite its advantages of not requiring additional training or hyperparameter tuning, and being applicable to any existing model, TTA is still in its early stages in the field of NLP. This is partly due to the difficulty of discerning the contribution of different transformed samples, which can negatively impact predictions. In order to address these issues, we propose Selective Test-Time Augmentation, called STTA, which aims to select the most beneficial transformed samples for aggregation by identifying reliable samples. Furthermore, we analyze and empirically verify why TTA is sensitive to some text data augmentation methods and reveal why some data augmentation methods lead to erroneous predictions. Through extensive experiments, we demonstrate that STTA is a simple and effective method that can produce promising results in various text classification tasks.

A Self-Healing Multifunctional Hydrogel System Accelerates Diabetic Wound Healing through Orchestrating Immunoinflammatory Microenvironment.

Developing an effective treatment strategy of drug delivery to improve diabetic wound healing remains a major challenge in clinical practice nowadays, due to multidrug-resistant bacterial infections, angiopathy, and oxidative damage in the wound microenvironment. Herein, an effective and convenient strategy was designed through a self-healing multiple-dynamic-bond cross-linked hydrogel with interpenetrating networks, which was formed by multiple-dynamic-bond cross-linking of reversible catechol-Fe3+ coordinate bonds, hydrogen bonding, and Schiff base bonds. The excellent autonomous healing of the hydrogel was initiated and accelerated by Schiff bonds with reversible breakage between 3,4-dihydroxybenzaldehyde containing catechol and aldehyde groups and chitosan chains, and further consolidated by the co-optation of other noncovalent interactions contributed of hydrogen bonding and Fe3+ coordinate bonds. Intriguingly, cathelicidin LL-37 was introduced and uniformly dispersed in the dynamic interpenetrating networks of the hydrogel as a bioactive molecular to orchestrate the diabetic wound healing microenvironment. This multifunctional wound dressing can significantly promote diabetic wound healing by antibacterial activity, immunomodulation, anti-inflammation, neovascularization, and antioxidant activity. Therefore, this study provided an effective and safe strategy for guiding the diabetic wound treatment in clinical applications.

Efficient Treatment of Pulpitis via Transplantation of Human Pluripotent Stem Cell-Derived Pericytes Partially through LTBP1-Mediated T Cell Suppression.

Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest. Then, we demonstrated that the ablation of pericytes could induce a pulpitis-like phenotype in uninfected dental pulp in mice, and we showed that the significant loss of pericytes occurs during pupal inflammation, implying that the transplantation of pericytes may help to restore dental pulp homeostasis during pulpitis. Subsequently, we successfully generated pericytes with immunomodulatory activity from human pluripotent stem cells through the intermediate stage of the cranial neural crest with a high level of efficiency. Most strikingly, for the first time we showed that, compared with the untreated pulpitis group, the transplantation of hPSC-derived pericytes could substantially inhibit vascular permeability (the extravascular deposition of fibrinogen, ** p < 0.01), alleviate pulpal inflammation (TCR+ cell infiltration, * p < 0.05), and promote the regeneration of dentin (** p < 0.01) in the mouse model of pulpitis. In addition, we discovered that the knockdown of latent transforming growth factor beta binding protein 1 (LTBP1) remarkably suppressed the immunoregulation ability of pericytes in vitro and compromised their in vivo regenerative potential in pulpitis. These results indicate that the transplantation of pericytes could efficiently rescue the aberrant phenotype of pulpal inflammation, which may be partially due to LTBP1-mediated T cell suppression.

Gut bacterial profiles in Parkinson's disease: A systematic review.

INTRODUCTION: Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD. METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls. RESULTS: Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions. CONCLUSION: Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.

A novel TIP30 protein complex regulates EGF receptor signaling and endocytic degradation.

Activated epidermal growth factor receptor (EGFR) continues to signal in the early endosome, but how this signaling process is regulated is less well understood. Here we describe a protein complex consisting of TIP30, endophilin B1, and acyl-CoA synthetase long chain family member 4 (ACSL4) that interacts with Rab5a and regulates EGFR endocytosis and signaling. These proteins are required for the proper endocytic trafficking of EGF-EGFR. Knockdown of TIP30, ACSL4, endophilin B1, or Rab5a in human liver cancer cells or genetic knock-out of Tip30 in mouse primary hepatocytes results in the trapping of EGF-EGFR complexes in early endosomes, leading to delayed EGFR degradation and prolonged EGFR signaling. Furthermore, we show that Rab5a colocalizes with vacuolar (H(+))-ATPases (V-ATPases) on transport vesicles. The TIP30 complex facilitates trafficking of Rab5a and V-ATPases to EEA1-positive endosomes in response to EGF. Together, these results suggest that this TIP30 complex regulates EGFR endocytosis by facilitating the transport of V-ATPases from trans-Golgi network to early endosomes.

Generation of a MSX1 knockout human embryonic stem cell line using CRISPR/Cas9 technology.

The MSX1 gene encodes a transcriptional repressor and plays important roles in limb-pattern formation, craniofacial development, and odontogenesis during vertebrate embryogenesis. Previous studies demonstrated that human MSX1 mutations are associated with tooth agenesis, orofacial clefting, and nail dysplasia. Here, we generated a MSX1 knockout cell line from human embryonic stem cell (hESC) line (H9) by CRISPR/cas9-mediated gene targeting. This cell line may serve as a valuable in vitro cell model for MSX1 mutation-related diseases and help to gain more insight into the biological function of MSX1.