Compulsivity-related behavioral features of problematic usage of the internet: A scoping review of paradigms, progress, and perspectives.

Background and aims: Compulsivity contributes to the development and maintenance of multiple addictive disorders. However, the relationship between compulsivity-related cognitive features and problematic usage of the internet (PUI), an umbrella term for various internet use disorders/interfering behaviors, remains largely unclear, partly due to the multidimensional nature of compulsivity. This scoping review utilized a four-domain framework of compulsivity to consider this topic and aimed to summarize available evidence on compulsivity-related neuropsychological characteristics in PUI based on this framework. Methods: A systematic literature search was conducted by applying the combination of search term to the search engines of PubMed, PsycINFO and Web of Science. A four-domain framework of compulsivity, involving cognitive flexibility, set-shifting, attentional bias, and habit learning, was used to consider its complex structure and frequently used tasks. Main findings in related PUI studies were summarized based on this framework. Our secondary aim was to compare compulsivity-related features between different PUI subtypes. Results: Thirty-four empirical studies were retained, comprising 41 task-results and 35 independent data sets. Overall, individuals with PUI showed more consistent deficits in attentional biases and were relatively intact in set-shifting. Few studies have examined cognitive flexibility and habit learning, and more evidence is thus needed to establish reliable conclusions. Moreover, most studies focused on internet gaming disorder, whereas other PUI sub-types were not sufficiently examined. Conclusion: This systematic review highlights the use of the four-domain framework for advancing understanding of mechanisms underlying compulsivity in PUI. Related therapeutic implications and future directions are discussed.

Genome-wide sequencing reveals geographical variations in the thermal adaptation of an aquaculture species with frequent seedling introductions.

Climate change and human activity are essential factors affecting marine biodiversity and aquaculture, and understanding the impacts of human activities on the genetic structure to increasing high temperatures is crucial for sustainable aquaculture and marine biodiversity conservation. As a commercially important bivalve, the Manila clam Ruditapes philippinarum is widely distributed along the coast of China, and it has been frequently introduced from Fujian Province, China, to other regions for aquaculture. In this study, we collected four populations of Manila clams from different areas to evaluate their thermal tolerance by measuring cardiac performance and genetic variations using whole-genome resequencing. The upper thermal limits of the clams showed high variations within and among populations. Different populations displayed divergent genetic compositions, and the admixed population was partly derived from the Zhangzhou population in Fujian Province, implying a complex genomic landscape under the influence of local genetic sources and human introductions. Multiple single nucleotide polymorphisms (SNPs) were associated with the cardiac functional traits, and some of these SNPs can affect the codon usage and the structural stability of the resulting protein. This study shed light on the importance of establishing long-term ecological and genetic monitoring programs at the local level to enhance resilience to future climate change.

Aggregation-Induced Emission Luminogens: A New Possibility for Efficient Visualization of RNA in Plants.

RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants' spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid-liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.

Ectopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma.

BACKGROUND: Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. METHODS: We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. RESULTS: The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. CONCLUSION: Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment.

Rujifang inhibits triple-negative breast cancer growth via the PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rujifang (RJF) constitutes a traditional Chinese medicinal compound extensively employed in the management of triple-negative breast cancer (TNBC). However, information regarding its potential active ingredients, antitumor effects, safety, and mechanism of action remains unreported. AIM OF THE STUDY: To investigate the efficacy and safety of RJF in the context of TNBC. MATERIALS AND METHODS: We employed the ultra high-performance liquid chromatography-electrospray four-pole time-of-flight mass spectrometry technique (UPLC/Q-TOF-MS/MS) to scrutinize the chemical constituents of RJF. Subcutaneously transplanted tumor models were utilized to assess the impact of RJF on TNBC in vivo. Thirty female BLAB/c mice were randomly divided into five groups: the model group, cyclophosphamide group, and RJF high-dose, medium-dose, and low-dose groups. A total of 1 × 106 4T1 cells were subcutaneously injected into the right shoulder of mice, and they were administered treatments for a span of 28 days. We conducted evaluations on blood parameters, encompassing white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), neutrophils, lymphocytes, and monocytes, as well as hepatorenal indicators including alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin, and creatinine (CRE) to gauge the safety of RJF. Ki67 and TUNEL were detected via immunohistochemistry and immunofluorescence, respectively. We prepared RJF drug-containing serum for TNBC cell lines and assessed the in vitro inhibitory effect of RJF on tumor cell growth through the CCK8 assay and cell cycle analysis. RT-PCR was employed to detect the mRNA expression of cyclin-dependent kinase and cyclin-dependent kinase inhibitors in tumor tissues, and Western blot was carried out to ascertain the expression of cyclin and pathway-related proteins. RESULTS: 100 compounds were identified in RJF, which consisted of 3 flavonoids, 24 glycosides, 18 alkaloids, 3 amino acids, 8 phenylpropanoids, 6 terpenes, 20 organic acids, and 18 other compounds. In animal experiments, both CTX and RJF exhibited substantial antitumor effects. RJF led to an increase in the number of neutrophils in peripheral blood, with no significant impact on other hematological indices. In contrast, CTX reduced red blood cell count, hemoglobin levels, and white blood cell count, while increasing platelet count. RJF exhibited no discernible influence on hepatorenal function, whereas Cyclophosphamide (CTX) decreased ALP, GOT, and GPT levels. Both CTX and RJF reduced the expression of Ki67 and heightened the occurrence of apoptosis in tumor tissue. RJF drug-containing serum hindered the viability of 4T1 and MD-MBA-231 cells in a time and concentration-dependent manner. In cell cycle experiments, RJF diminished the proportion of G2 phase cells and arrested the cell cycle at the S phase. RT-PCR analysis indicated that RJF down-regulated the mRNA expression of CDK2 and CDK4, while up-regulating that of P21 and P27 in tumor tissue. The trends in CDKs and CDKIs protein expression mirrored those of mRNA expression. Moreover, the PI3K/AKT pathway displayed downregulation in the tumor tissue of mice treated with RJF. CONCLUSION: RJF demonstrates effectiveness and safety in the context of TNBC. It exerts anti-tumor effects by arresting the cell cycle at the S phase through the PI3K-AKT pathway.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Infrared Photodissociation Spectroscopy of Mass-Selected Dinuclear Transition Metal Boride Carbonyl Cluster Cations.

The transition-metal-boron bonding interactions and geometric structures of heterodinuclear transition metal carbonyl cluster cations BM(CO)n+ (M = Co, Ni, and Cu) are studied by a combination of the infrared photodissociation spectroscopy and density functional theory calculations at the B3LYP/def2-TZVP level. The BCu(CO)5+ and BCo(CO)6+ cations are characterized as an (CO)2B-M(CO)3/4+ structure involving an σ-type (OC)2B → M(CO)3,4+ dative bonding with end-on carbonyls, while for BNi(CO)5,6+ complexes with a bridged carbonyl, a 3c-2e bond involving the 5σ electrons of the bridged carbonyl and an electron-sharing bond between the B(CO)2 fragment and the Ni(CO)2,3+ subunits were revealed. Moreover, the fundamental driving force of the exclusive existence of a bridged carbonyl group in the boron-nickel complexes has been demonstrated to stem from the desire of the B and Ni centers for the favorable 8- and 18-electron structures.

In situ bio-mineralized Mn nanoadjuvant enhances anti-influenza immunity of recombinant virus-like particle vaccines.

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist Mn3O4 inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating. Such inside Mn3O4 immunostimulator-outside rHA antigen design, together with the chimeric M2e antigen on the HBc skeleton, enabled the synthesized hybrid nanovaccines THM-HA@Mn to well imitate the spatial distribution of M2e/HA antigens and immunostimulant in natural influenza virus. In vitro cellular experiments indicated that compared with the THM-HA antigen without Mn3O4 and a mixture vaccine consisting of THM-HA + MnOx, the THM-HA@Mn hybrid nanovaccines showed the highest efficacies in dendritic cells uptake and in promoting BMDC maturation, as well as inducing expression of TNF-α and type I interferon IFN-ß. The THM-HA@Mn also displayed the most sustained antigen release at the injection site, the highest efficacies in promoting the DC maturation in lymph nodes and germinal center B cells activation in the spleen of the immunized mice. The co-delivery of immunostimulant and antigens enabled the THM-HA@Mn nanovaccines to induce the highest systemic antigen-specific antibody responses and cellular immunogenicity in mice. Together with the excellent colloid dispersion stability, low cytotoxicity, as well as good biosafety, the synthetic hybrid nanovaccines presented in this study offers a promising strategy to design VLP-based vaccine with robust natural and adaptive immunogenicity against emerging viral pathogens.

Antigen/HLA-agnostic strategies for Characterizing Tumor-responsive T cell receptors in PDAC patients via single-cell sequencing and autologous organoid application.

Characterization of tumor-responsive T cell receptors (TCRs) is a critical step in personalized TCR-T cell therapy, and remains challenging for pancreatic ductal adenocarcinoma (PDAC). Here we report a proof-of-concept study to identify and validate antitumor TCRs in two representative PDAC patients using ultradeep single-cell TCR/RNA sequencing and autologous organoids, and reveal the phenotypic dynamics of TCR repertoire in different T cell expansions from the same patient. We first performed comparative sequencing on freshly harvested peripheral blood mononuclear cells (PBMCs) and uncultured tumor infiltrating lymphocytes (TILs), followed by reactivity tests of TIL-enriched TCRs with autologous organoids, in which two tumor-responsive TCRs were successfully characterized and the corresponding TILs were mostly tissue-resident memory-like T cells, and partially expressed both naïve and exhausted T cell markers. For the PDAC patient without high-quality TILs, PBMCs were cultured with neoantigen peptide (KRASG12D), organoids, or anti-CD3 antibody in presence, and experienced extensive clonal expansions within ten days. All derived PBMCs were sequenced in parallel (>82,000 cells), and TCRs enriched in both peptide- and organoid-experienced, but not anti-CD3-treated CD8 T cells, were assessed for their reactivity to antigen-presenting cells (APCs) and organoids, in which three neoantigen-reactive TCRs were identified as tumor-responsive, and the corresponding T cells were characterized by mixed transcriptional signatures including but not limited to typical exhausted T cell markers. Together, our study revealed that the combination of ultradeep single-cell sequencing and organoid techniques enabled rapid characterization of tumor-responsive TCRs for developing practical personalized TCR-T therapy in an antigen/human leukocyte antigen (HLA)-agnostic manner.

Characterization of aroma-active compounds in sesame hulls at different roasting temperatures by SAFE and GC-O-MS.

The study characterized the aroma-active compounds produced by sesame hulls at three roasting temperatures and analyzed the similarities and differences in the aroma profile of sesame hulls with whole seeds and kernels after roasting. Roasting hulls produced mainly furans, aldehydes, and ketones volatiles. 140 Compounds were identified as aroma-active compounds, including 36 key aroma compounds (odor activity value, OAV ≥ 1). Among them, furanone (caramel-like, OAV = 80), 3-methylbutanal (fruity, OAV = 124), and 2-methoxy-4-vinylphenol (burnt, smoky, OAV = 160) gave hulls (180 °C) sweet, burnt, and smoky aroma. Due to the contribution of vanillin (fatty, sweet milk, OAV = 45), 2-hydroxy-3-butanone (caramel-like, roast, OAV = 46), and 2-methoxy-4-vinylphenol (OAV = 78), hulls (200 °C) shown strong sweet and roast note. These results identified compounds that contributed significantly to the aroma of sesame hulls and elucidated the contribution of sesame hulls to the flavor of roasted whole seeds and sesame oil.

GPC2 as a diagnostic and prognostic marker regulated progression of colorectal cancer.

BACKGROUND AND STUDY AIMS: Glypican 2 (GPC2) is a member of the glypican gene family and is expressed in multiple kinds of cancer. However, the function and mechanism of GPC2 in colorectal cancer remains unclear. In this study, we aimed to identify the role of GPC2 on tumor cell proliferation and survival in colorectal cancer. PATIENTS AND METHODS: Ten pairs of colon cancer and matched normal colon tissues were collected in this research. GEPIA was used to analysis the GPC2 gene expression profile in TGCA data base. RT-qPCR and western blot assay were performed to determine the mRNA and protein expressions. CCK-8, Flow cytometry and colon formation assay were applied to evaluate cell viability. IHC staining was performed to evaluate the protein expression in tissues. The function of GPC2 in vivo was verified by an animal model of colon cancer. RESULTS: Through the bioinformatics analysis and qRT-PCR validation, we found that GPC2 was upregulated in the colon cancer tissues and cells. GPC2 knockdown suppressed cell proliferation in vitro and in vivo was confirmed by the results of CCK-8, colony formation assays, and tumor xenograft models. Moreover, by the analysis of flow cytometry assay and gain-or-loss function experiments, we discovered that CEP164 was highly associated with the expression state of GPC2, and mediated G2/M-phase arrest in GPC2-downregulated tumor cells. CONCLUSION: GPC2 might be a novel oncogenic gene in colorectal cancer, suggesting that it could be a considerable marker for the diagnosis and prognosis of colorectal cancer.

Association between ethylene oxide levels and depressive symptoms: A cross-sectional study based on NHANES 2013-2018 database.

BACKGROUND AND AIM: Ethylene oxide (EO) is a commonly used compound with known health risks. However, the specific association between EO exposure and the development of depressive symptoms has not been well established. Therefore, this study aimed to examine the potential association between EO exposure, as indicated by hemoglobin adduct of ethylene oxide (HbEO) levels, and the occurrence of depressive symptoms. METHODS: We employed logistic regression, restricted cubic spline, and subgroup analysis to investigate the association between EO exposure and the occurrence of depressive symptoms. Additionally, we conducted a mediating effect analysis to explore the potential factors influencing the association between EO exposure and depressive symptoms. RESULTS: Elevated HbEO levels were associated with the development of depressive symptoms. After adjusting for potential confounders, the highest quartile of HbEO levels showed an odds ratio (OR) of 3.37 [95 % confidence interval (CI): 1.87-6.10, P = 0.002] compared with the lowest quartile. Additionally, a linear association was observed between HbEO levels and the risk of depressive symptoms. We also revealed that the levels of several inflammatory factors and triglycerides mediated the association between EO exposure and the occurrence of depressive symptoms. CONCLUSIONS: Higher levels of EO exposure were related to an increased risk of developing depressive symptoms. The analysis also suggested that the inflammatory response might play a mediating role in the pathway from EO exposure to depressive symptoms.

Evaluation of species thermal sensitivity with individual-based physiological performance.

Ignoring intraspecific variations can prevent us from accurately assessing species' thermal sensitivity to global warming. Individual-based physiological performance provides a feasible solution to depict species' thermal sensitivity using a bottom-up approach. We measured the cardiac performance of intertidal bivalves (1159 individuals from multiple populations of six bivalves), determined the upper thermal limit of each individual, calculated the proportions of individuals suffering sublethal/lethal heat stress, and mapped sensitive regions to high temperatures. Results showed that high inter-individual variations of physiological performance existed in levels of populations and species, and species' thermal sensitivity was positively related to the intraspecific variations of heat tolerance. This bottom-up approach scaled up from individual, population to species emphasizes the importance of individual-based physiology performance in assessing thermal sensitivity across different hierarchical levels and enables better evaluating and forecasting of species responses to global warming.

Prediction of multi-relational drug-gene interaction via Dynamic hyperGraph Contrastive Learning.

Drug-gene interaction prediction occupies a crucial position in various areas of drug discovery, such as drug repurposing, lead discovery and off-target detection. Previous studies show good performance, but they are limited to exploring the binding interactions and ignoring the other interaction relationships. Graph neural networks have emerged as promising approaches owing to their powerful capability of modeling correlations under drug-gene bipartite graphs. Despite the widespread adoption of graph neural network-based methods, many of them experience performance degradation in situations where high-quality and sufficient training data are unavailable. Unfortunately, in practical drug discovery scenarios, interaction data are often sparse and noisy, which may lead to unsatisfactory results. To undertake the above challenges, we propose a novel Dynamic hyperGraph Contrastive Learning (DGCL) framework that exploits local and global relationships between drugs and genes. Specifically, graph convolutions are adopted to extract explicit local relations among drugs and genes. Meanwhile, the cooperation of dynamic hypergraph structure learning and hypergraph message passing enables the model to aggregate information in a global region. With flexible global-level messages, a self-augmented contrastive learning component is designed to constrain hypergraph structure learning and enhance the discrimination of drug/gene representations. Experiments conducted on three datasets show that DGCL is superior to eight state-of-the-art methods and notably gains a 7.6% performance improvement on the DGIdb dataset. Further analyses verify the robustness of DGCL for alleviating data sparsity and over-smoothing issues.

Diverse electron carriers drive syntrophic interactions in an enriched anaerobic acetate-oxidizing consortium.

In many anoxic environments, syntrophic acetate oxidation (SAO) is a key pathway mediating the conversion of acetate into methane through obligate cross-feeding interactions between SAO bacteria (SAOB) and methanogenic archaea. The SAO pathway is particularly important in engineered environments such as anaerobic digestion (AD) systems operating at thermophilic temperatures and/or with high ammonia. Despite the widespread importance of SAOB to the stability of the AD process, little is known about their in situ physiologies due to typically low biomass yields and resistance to isolation. Here, we performed a long-term (300-day) continuous enrichment of a thermophilic (55 °C) SAO community from a municipal AD system using acetate as the sole carbon source. Over 80% of the enriched bioreactor metagenome belonged to a three-member consortium, including an acetate-oxidizing bacterium affiliated with DTU068 encoding for carbon dioxide, hydrogen, and formate production, along with two methanogenic archaea affiliated with Methanothermobacter_A. Stable isotope probing was coupled with metaproteogenomics to quantify carbon flux into each community member during acetate conversion and inform metabolic reconstruction and genome-scale modeling. This effort revealed that the two Methanothermobacter_A species differed in their preferred electron donors, with one possessing the ability to grow on formate and the other only consuming hydrogen. A thermodynamic analysis suggested that the presence of the formate-consuming methanogen broadened the environmental conditions where ATP production from SAO was favorable. Collectively, these results highlight how flexibility in electron partitioning during SAO likely governs community structure and fitness through thermodynamic-driven mutualism, shedding valuable insights into the metabolic underpinnings of this key functional group within methanogenic ecosystems.

Lifestyle interventions to prevent adverse pregnancy outcomes in women at high risk for gestational diabetes mellitus: a randomized controlled trial.

Objective: To examine the effects of lifestyle interventions, including dietary guidance, health education and weight management, on pregnancy outcomes in women at high risk of gestational diabetes mellitus (GDM). Methods: Our study included 251 women at high risk of GDM and 128 randomized to lifestyle interventions (dietary guidance, health education, and weight management); One hundred and twenty-three people were randomly assigned to a control group (regular pregnancy check-ups). Counts between groups were compared using either chi-square test or Fisher's exact test. Results: Compared with the control group, the risk of GDM was reduced by 46.9% (16.4% vs 30.9%, P = 0.007) and the risk of pregnancy induced hypertension (PIH) was reduced by 74.2% (2.3% vs 8.9%, P = 0.034) in the intervention group. There were no significant differences in macrosomia, cesarean section, or preterm birth (P >0.05). Conclusion: The lifestyle intervention in this study helped pregnant women to better understand knowledge related to pregnancy, reduce stress and anxiety, and increase intake of adequate prenatal nutrition. This intervention prevented metabolic abnormalities that may occur due to inadequate nutrient intake during pregnancy. In addition, it helped women to control weight gain, maintain appropriate weight gain during pregnancy, and reduce the risk of excessive or insufficient weight gain, ultimately lowering the incidence of GDM and PIH. This highlights the importance of early screening and intervention for high-risk pregnant women. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2300073766.

[Microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle].

OBJECTIVE: To explore method and clinical effect of microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle. METHODS: From March 2017 to January 2022, totally 20 patients with soft tissue defects of ankle joint were treated with micro-thinning anterolateral perforator flap for free transplantation, included 13 males and 7 females, aged from 22 to 58 years old with an average of (36.45±12.36) years old. The size of flap ranged from 8.0 cm×5.0 cm to 20.0 cm×12.0 cm. Before operation, perforating vessels on the anterolateral thigh region were detected and marked with a portable Doppler detector. For the defect width less than 8 cm, 11 patients were repaired with a single flap. For the defect width more than 8 cm, the wound could not be sutured directly, and the lobulated flap technique was used in 9 patients, the width was converted to length, and the donor site was closed directly. Under the microscope, all flaps were thinened in a stepwise manner from the center of the pedicle to the periphery. After operation, survival of the flap, the shape, texture, sensory function recovery were observes, and recovery of foot function was evaluated by Maryland foot function evaluation standard. RESULTS: All 20 patients with microsurgical thinned anterolateral thigh perforator flaps were survived. Venous crisis occurred in 1 patient due to subcutaneous hematoma, after removal of the hematoma, the crisis was relieved and the flap survived successfully. The wounds in the donor and recipient sites healed well, and only linear scars left in the donor sites. Twenty patients were followed up for 3 to 26 months after operation, good shape of flaps without bloated, and good texture. The two-point discrimination of free flaps ranged from 9.0 to 16.0 mm, and the protective sensation was restored. The ankle flexion and extension function recovered well and patients could walk normally. According to Maryland foot function evaluation standard, 8 patients got excellent result, 10 patients good and 2 middle. CONCLUSION: Microsurgical thinned anterolateral thigh perforator flap is an ideal method to repair soft tissue defects in functional area of foot and ankle, with good appearance and texture of the flap, no need for re-plastic surgery, reduced hospitalization costs, and less donor site damage.

The TRIM37 variants in Mulibrey nanism patients paralyze follicular helper T cell differentiation.

The Mulibrey (Muscle-liver-brain-eye) nanism caused by loss-of-function variants in TRIM37 gene is an autosomal recessive disorder characterized by severe growth failure and constrictive pericarditis. These patients also suffer from severe respiratory infections, co-incident with an increased mortality rate. Here, we revealed that TRIM37 variants were associated with recurrent infection. Trim37 FINmajor (a representative variant of Mulibrey nanism patients) and Trim37 knockout mice were susceptible to influenza virus infection. These mice showed defects in follicular helper T (TFH) cell development and antibody production. The effects of Trim37 on TFH cell differentiation relied on its E3 ligase activity catalyzing the K27/29-linked polyubiquitination of Bcl6 and its MATH domain-mediated interactions with Bcl6, thereby protecting Bcl6 from proteasome-mediated degradation. Collectively, these findings highlight the importance of the Trim37-Bcl6 axis in controlling the development of TFH cells and the production of high-affinity antibodies, and further unveil the immunologic mechanism underlying recurrent respiratory infection in Mulibrey nanism.