The complete chloroplast genome of Hemiboea pterocaulis (Gesneriaceae) exclusively distributed in Guilin, Guangxi, China.

Hemiboea pterocaulis is a unique species only found in Guilin, Guangxi, China. In this study, we sequenced and assembled the complete chloroplast genome of H. pterocaulis and revealed its phylogenetic relationship with other Hemiboea species. The chloroplast genome sequence of H. pterocaulis is 153,159 bp in length and comprises a large single-copy (LSC) region of 84,178 bp, a small single-copy (SSC) region of 18,087 bp, and a pair of inverted repeat (IR) regions, each with a length of 25,447 bp. It has a total GC content of 37.6% and encodes 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships based on the complete chloroplast genome sequences of Hemiboea taxa indicate that H. pterocaulis is most closely related to H. suiyangensis, indicating that H. pterocaulis is an independent species and is separated from the H. subcapitata complex. These results provide valuable insights into the phylogeny, species divergence, and delimitation of the Hemiboea genus.

Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6.

BACKGROUND: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. OBJECTIVES: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. METHODS: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. RESULTS: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient's atopic dermatitis. CONCLUSIONS: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.

Autoinhibitory structure of preligand association state implicates a new strategy to attain effective DR5 receptor activation.

Members of the tumor necrosis factor receptor superfamily (TNFRSF) are important therapeutic targets that can be activated to induce death of cancer cells or stimulate proliferation of immune cells. Although it has long been implicated that these receptors assemble preligand associated states that are required for dominant interference in human disease, such states have so far eluded structural characterization. Here, we find that the ectodomain of death receptor 5 (DR5-ECD), a representative member of TNFRSF, can specifically self-associate when anchored to lipid bilayer, and we report this self-association structure determined by nuclear magnetic resonance (NMR). Unexpectedly, two non-overlapping interaction interfaces are identified that could propagate to higher-order clusters. Structure-guided mutagenesis indicates that the observed preligand association structure is represented on DR5-expressing cells. The DR5 preligand association serves an autoinhibitory role as single-domain antibodies (sdAbs) that partially dissociate the preligand cluster can sensitize the receptor to its ligand TRAIL and even induce substantial receptor signaling in the absence of TRAIL. Unlike most agonistic antibodies that require multivalent binding to aggregate receptors for activation, these agonistic sdAbs are monovalent and act specifically on an oligomeric, autoinhibitory configuration of the receptor. Our data indicate that receptors such as DR5 can form structurally defined preclusters incompatible with signaling and that true agonists should disrupt the preligand cluster while converting it to signaling-productive cluster. This mechanism enhances our understanding of a long-standing question in TNFRSF signaling and suggests a new opportunity for developing agonistic molecules by targeting receptor preligand clustering.

Ultrasound Assessment of the Relevance of Liver, Spleen, and Kidney Dimensions with Body Parameters in Adolescents.

Objective: Ultrasound is a practical imaging modality for screening and identification of anomalies in the organs. This study used ultrasonography to examine the association between body parameters and dimensions of the normal liver, spleen, and kidney in adolescents based on ultrasound examination results. Methods: A total of 300 junior and senior high school teenagers receiving routine health check-ups in our hospital from January 2020 to January 2021 were included. Their height and weight were measured, and their body surface area (BSA) and body mass index (BMI) were calculated. Ultrasound imaging was employed to obtain information such as the length and volume of the liver, gallbladder, spleen, and kidney. Besides, the correlation of body parameters such as gender, age, height, weight, BSA, and BMI with visceral dimension was investigated using the Pearson test and multiple regression analysis, respectively. Results: We observed that the abdominal organs of adolescents were enlarged with age. The span and volume of the liver and the length and volume of the right kidney were significantly larger in boys than in girls. The age, BSA, and BMI were positively correlated with the liver span and spleen length, as well as the left and right kidney lengths. Additionally, age, BSA, and BMI were identified as important predictors for dimensions of the spleen, liver, and kidney. Conclusions: Body parameters are notably associated with the dimensions of the liver, spleen, and kidney and could be utilized as predicting factors for the liver, spleen, and kidney dimensions.

Fabrication of ZnAl-LDH mixed metal-oxide composites for photocatalytic degradation of 4-chlorophenol.

In this work, two different types of ZnAl-layered double hydroxide (LDH) mixed metal-oxide composites (CeO2 and SnO2) were synthesized and applied for the photodegradation of 4-chlorophenol (4-CP) in wastewater. The fabricated CeO2/ZnAl-LDH and SnO2/ZnAl-LDH were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV-visible diffuse reflectance spectroscopy (UV-vis DRS), and theoretical density functional theory (DFT) calculations, suggesting that the band gaps of the synthesized hybrid composites were much lower than those of traditional ZnAl-LDH. In addition, the photocatalytic activity for 4-CP degradation and reaction kinetics were investigated to evaluate the catalytic behavior of the prepared composites. The results indicated that the photocatalytic process in this case followed a pseudo-first-order kinetic model, and SnO2/ZnAl-LDH illustrated the optimum performance for 4-CP degradation with an efficiency of 95.2% due to its stability and recyclability. Additionally, the reaction mechanism of 4-CP photodegradation was studied over SnO2/ZnAl-LDH; it presented that 4-CP could be oxidized by hydroxyl radicals, holes, and superoxide radicals, where hydroxyl radicals were identified as the dominant active species during the degradation process. Finally, decomposition intermediates were measured to deduce the reaction pathway of 4-CP, and three tentative pathways were proposed and discussed.

Interaction of magnolia bark extracts with Staphylococcus aureus DNA and evaluation of the stability of their antibacterial activities.

Magnolia bark is an edible traditional Chinese medicine that has antibacterial activity against Staphylococcus aureus. In the present study, interactions between S. aureus DNA and raw magnolia bark (RMB) and ginger mix-fried magnolia bark (GMB) aqueous extracts were determined via spectroscopic methods. Fluorescence spectroscopy and Stern-Volmer constants showed that S. aureus DNA quenched the fluorescence of the extracts by static quenching. UV-Vis spectroscopy and iodide quenching experiments indicated that the interactions between S. aureus DNA and the fluorescent substances might involve groove binding or electrostatic interactions. In 4', 6-diamidino-2-phenylindole competitive assays, the fluorescence intensity at decreased as the extract amount was increased. This indicates that groove binding is responsible for the fluorescence quenching. The antibacterial activity of GMB aqueous extract treated under light, cold, heat and cycling hot-cold conditions decreased by 13.99, 9.31, 10.89 and 14.40%, respectively, whereas that of RMB aqueous extract treated under the same conditions decreased by 8.91, 14.99, 14.99 and 13.70%, respectively. The results indicate that S. aureus DNA quenches the fluorescence of GMB and RMB aqueous extracts by grooving interactions. Additionally, the antibacterial activities of GMB and RMB extracts are sensitive to light and temperature, respectively.

Structures and functions of the inflammasome engine.

Inflammasomes are molecular machines that carry out inflammatory responses on challenges by pathogens and endogenous dangers. Dysregulation of inflammasome assembly and regulation is associated with numerous human diseases from autoimmunity to cancer. In recent years, significant advances have been made in understanding the mechanism of inflammasome signaling using structural approaches. Here, we review inflammasomes formed by the NLRP1, NLRP3, and NLRC4 sensors, which are well characterized structurally, and discuss the structural and functional diversity among them.

High-Grade B-Cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 Rearrangements Is Predominantly BCL6-Rearranged and BCL6-Expressing in Taiwan.

This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

[Therapeutic effect of Wei's triple nine needling combined with medication on optic atrophy].

OBJECTIVE: To explore the effect of Wei 's triple nine needling on visual acuity and visual field in patients with optic atrophy. METHODS: A total of 90 patients with optic atrophy were randomized into an observation group and a control group, 45 cases in each one. Treatment of Wei 's triple nine needling combined with conventional medication were adopted in the observation group, conventional medication was given in the control group. Treatment for 4 weeks was required in both groups. Before treatment and 2, 4 weeks into treatment, the visual acuity and visual field were observed, and the clinical efficacy was evaluated in both groups. RESULTS: The total effective rate was 57.8% (26/45) in the observation group, which was superior to 28.9% (13/45) in the control group (P<0.05). After 2-week and 4-week treatment, the visual acuity was improved (P<0.01), the mean defect (MD) of visual field was decreased (P<0.01), the mean sensitivity (MS) of visual field was increased in the observation group (P<0.05, P<0.01). After 2-week and 4-week treatment, the visual acuity and the MD of visual field were improved (P<0.01, P<0.05), while the difference of MS of visual field compared before treatment had no statistical significance in the control group (P>0.05). The improvement of visual acuity, MD and MS of visual field after 2-week and 4-week into treatment in the observation group were superior to those in the control group (P<0.05, P<0.01). CONCLUSION: Wei 's triple nine needling can effectively improve the visual acuity and the defect of visual field in patients with optic atrophy.

Skin bacterial structure of young females in China: The relationship between skin bacterial structure and facial skin types.

BACKGROUND: Skin microbiota are involved in the skin physiological functions and are also affected by the skin physiological characteristics. OBJECTIVE: To better understand the skin microbial characteristics of facial cheek skin and the relationship with skin physiological characteristics. METHODS: By bacterial 16S rRNA gene sequencing, the authors studied the facial cheek skin microbial characteristics of 85 cases of young women aged 18-25 years. RESULTS: Healthy young woman's cheek skin bacterial composition was relatively stable. Dry skin has high bacterial diversity and richness, and oily skin has low bacterial diversity and richness. Cutibacterium was significantly enriched in oily skin and was significantly negatively correlated with other genera such as Streptococcus (r > 0.5). There were significant positive correlations among other genera of enrichment in dry and neutral skin such as Streptococcus and Rothia (r > 0.8). Skin sebum level was significantly negatively correlated with bacterial alpha diversity index. The combined abundance of Cutibacterium acnes and Staphylococcus epidermidis was significantly positively correlated with sebum secretion (r > 0.5). CONCLUSIONS: The skin sebum secretion and bacterial interaction were the important factors driving the young females' cheek skin bacterial community structure.

A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits.

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargo to the membrane-bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we report a selective autophagy pathway for protein condensates formed by endocytic proteins in yeast. In this pathway, the endocytic protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis and does not involve other known selective autophagy receptors but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates, at the plasma membrane and in autophagic bodies, shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy route. Our data suggest a model for autophagic degradation of macromolecular protein complexes by the action of intrinsic autophagy receptors.

Astragalus Polysaccharide (PG2) Suppresses Macrophage Migration Inhibitory Factor and Aggressiveness of Lung Adenocarcinoma Cells.

Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.

Tissue-Specific Regulation of the Wnt/ß-Catenin Pathway by PAGE4 Inhibition of Tankyrase.

Spatiotemporal control of Wnt/ß-catenin signaling is critical for organism development and homeostasis. The poly-(ADP)-ribose polymerase Tankyrase (TNKS1) promotes Wnt/ß-catenin signaling through PARylation-mediated degradation of AXIN1, a component of the ß-catenin destruction complex. Although Wnt/ß-catenin is a niche-restricted signaling program, tissue-specific factors that regulate TNKS1 are not known. Here, we report prostate-associated gene 4 (PAGE4) as a tissue-specific TNKS1 inhibitor that robustly represses canonical Wnt/ß-catenin signaling in human cells, zebrafish, and mice. Structural and biochemical studies reveal that PAGE4 acts as an optimal substrate decoy that potently hijacks substrate binding sites on TNKS1 to prevent AXIN1 PARylation and degradation. Consistently, transgenic expression of PAGE4 in mice phenocopies TNKS1 knockout. Physiologically, PAGE4 is selectively expressed in stromal prostate fibroblasts and functions to establish a proper Wnt/ß-catenin signaling niche through suppression of autocrine signaling. Our findings reveal a non-canonical mechanism for TNKS1 inhibition that functions to establish tissue-specific control of the Wnt/ß-catenin pathway.

Skin surface lipidomics revealed the correlation between lipidomic profile and grade in adolescent acne.

BACKGROUND: Acne is a multifactorial skin disorder frequently observed during adolescence with different grades of severity. The crucial factors of acne are the increase of lipids secretion and the change of composition on the skin surface lipid (SSL). However, there are no studies on the changes of lipid composition and content between different grades of adolescent acne in lesional skin and nonlesionsal skin. AIMS: This study was to investigate correlation in the composition of SSL and different grades in order to understand the tendency of SSL alterations in this disease for successful acne management and prevention. METHODS: A powerful analytical technique, UPLC-QTOF-MS, and multivariate data analysis were used to investigate SSL variations of lipid main classes, subclasses, and species. RESULTS: The results indicated that sphinganine, triradylglycerols (TG), and phytosphingosine were important in adolescent acne development. The average fatty acids (FAs) chain length in patients with acne showed significantly shortened trend from mild to moderate adolescent acne. Additionally, the relative average content of TG, diglyceride (DG), FA, ceramides (Cers), and the level of unsaturated FAs significantly increased from mild to moderate adolescent acne. Interestingly, our results demonstrated that the phytosphingosine and sphinganine showed an increasing trend in mild acne groups, but decreasing trend in lesional skin of moderate group. CONCLUSIONS: Lipidomics analysis suggested that the variation of TG, phytosphingosine, and sphinganine was closely related to the occurrence severity of acne in adolescent.

Cheek Microbial Communities Vary in Young Children with Atopic Dermatitis in China.

BACKGROUND: Atopic dermatitis (AD) is a chronic, recurrent skin condition with recently increased incidence in younger children. AD development has been correlated with the skin microbiome, and Staphylococcus aureus enrichment causes significant increases in skin lesions. OBJECTIVE: Our objectives were to compare the microbial diversity of the cheek skin of children with or without AD aged 0-1 years in China, and to determine whether 4 types of skin-isolated bacteria could inhibit S. aureus in vitro. METHODS: The skin microbial samples of cheek skin of children were sequenced by 16S rRNA V1-V2 region. Four skin isolated bacterial fermentation supernatants were tested for effects on S. aureus growth, membrane formation, and induction of cytokine secretion from HaCaT cells. RESULTS: Bacterial diversity decreased significantly in skin with severe AD compared to healthy skin (p < 0.01). Seven phyla had content >1%, 4 of which differed in AD (p < 0.05). 38 genera had content >1%, 15 differed (p < 0.05). Differences in 8 species were observed (p < 0.05). In vitro antibacterial and cellular experiments showed that S. aureus growth, biofilm formation, and induction of interleukin (IL)-1α and IL-6 secretion from HaCaT cells were significantly inhibited by Klebsiella oxytoca, Kocuria rhizophila, and Staphylococcus epidermidis culture supernatants (p < 0.05). CONCLUSION: Skin microbiome changes in children varied with age and with AD. There were complex interactions between skin isolated bacteria and S. aureus which could inhibit S. aureus growth and biofilm formation in vitro, suggesting that these microorganisms could be used in AD treatment.

Allosteric regulation through a switch element in the autophagy E2, Atg3.

Lipidation of Atg8-family ubiquitin-like proteins (UBLs) plays important roles in macroautophagy/autophagy. This process is catalyzed by an E1-E2-E3 trienzyme cascade, in which an E1 enzyme, Atg7, directs Atg8 to its E2 enzyme, Atg3, forming a thioester bond-linked Atg3~ Atg8 intermediate; then the composite E3, Atg12-Atg5-Atg16, interacts with the Atg3~ Atg8 intermediate and promotes Atg8 transfer from the catalytic cysteine of Atg3 to the head group of phosphatidylethanolamine (PE) lipids. Despite progress that has been made toward understanding the Atg8 lipidation pathway, the molecular mechanism of Atg3 as it orchestrates between the E1 and E3 remains unclear. Here we summarize our recent work reporting an element in Atg3, termed the E1, E2, and E3-interacting region (E123IR), is an allosteric switch: in the absence of other binding partners, the E123IR restrains Atg3's catalytic loop, while the E1 or E3 enzyme directly binds this region to remove this brace and thereby conformationally activate Atg3 to elicit Atg8 lipidation in vitro and in vivo.

Shifts in the skin microbiome associated with diaper dermatitis and emollient treatment amongst infants and toddlers in China.

BACKGROUND: The microbiological basis of diaper dermatitis has not been clearly elucidated; however, a better understanding of microbial colonization may be vital for developing appropriate therapies. METHODS: Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities obtained from the buttock skin sites of children with diaper dermatitis and from healthy controls. Bacterial diversity in the buttock lesion area and subsequent recovery after emollient treatment have been discussed herein. RESULTS: In buttock skin of children with or without diaper dermatitis, Staphylococcus and Anaerococcus were predominant in the total skin microbiome. Compared with the healthy group, the overall skin bacterial richness and diversity were higher in children with diaper dermatitis, with the abundance of Proteobacteria being significantly higher. In the diaper dermatitis group, the richness of Enterococcus, Erwinia and Pseudomonas was significantly higher, and the levels of Clostridium and Actinomyces were significantly lower than those in healthy children. Richness of Staphylococcus aureus was significantly higher in the diaper dermatitis group, whereas that of Staphylococcus epidermidis and Bifidobacterium longum was lower. Staphylococcus epidermidis and Staphylococcus haemolyticus, the dominant species found in buttock skin, were observed to recover earlier after the disease had improved through emollient treatment. CONCLUSION: Staphylococcus epidermidis, as skin probiotic bacterium, and B longum, Clostridium butyricum and Lactobacillus ruminis, which are intestinal probiotic bacteria, are significantly decreased in diaper dermatitis lesions. These changes in the buttock skin microflora indicate an imbalance in the microflora and suggest that the intestinal microflora may be undergoing dynamic changes. The results of this study suggest that probiotic bacterial supplementation may be useful in the treatment and prevention of diaper dermatitis.

A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade.

Autophagy depends on the E2 enzyme, Atg3, functioning in a conserved E1-E2-E3 trienzyme cascade that catalyzes lipidation of Atg8-family ubiquitin-like proteins (UBLs). Molecular mechanisms underlying Atg8 lipidation remain poorly understood despite association of Atg3, the E1 Atg7, and the composite E3 Atg12-Atg5-Atg16 with pathologies including cancers, infections and neurodegeneration. Here, studying yeast enzymes, we report that an Atg3 element we term E123IR (E1, E2, and E3-interacting region) is an allosteric switch. NMR, biochemical, crystallographic and genetic data collectively indicate that in the absence of the enzymatic cascade, the Atg3E123IR makes intramolecular interactions restraining Atg3's catalytic loop, while E1 and E3 enzymes directly remove this brace to conformationally activate Atg3 and elicit Atg8 lipidation in vitro and in vivo. We propose that Atg3's E123IR protects the E2~UBL thioester bond from wayward reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site remodeling through an unprecedented mechanism to drive autophagy.