UTX condensation underlies its tumour-suppressive activity.

UTX (also known as KDM6A) encodes a histone H3K27 demethylase and is an important tumour suppressor that is frequently mutated in human cancers1. However, as the demethylase activity of UTX is often dispensable for mediating tumour suppression and developmental regulation2-8, the underlying molecular activity of UTX remains unknown. Here we show that phase separation of UTX underlies its chromatin-regulatory activity in tumour suppression. A core intrinsically disordered region (cIDR) of UTX forms phase-separated liquid condensates, and cIDR loss caused by the most frequent cancer mutation of UTX is mainly responsible for abolishing tumour suppression. Deletion, mutagenesis and replacement assays of the intrinsically disordered region demonstrate a critical role of UTX condensation in tumour suppression and embryonic stem cell differentiation. As shown by reconstitution in vitro and engineered systems in cells, UTX recruits the histone methyltransferase MLL4 (also known as KMT2D) to the same condensates and enriches the H3K4 methylation activity of MLL4. Moreover, UTX regulates genome-wide histone modifications and high-order chromatin interactions in a condensation-dependent manner. We also found that UTY, the Y chromosome homologue of UTX with weaker tumour-suppressive activity, forms condensates with reduced molecular dynamics. These studies demonstrate a crucial biological function of liquid condensates with proper material states in enabling the tumour-suppressive activity of a chromatin regulator.

GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor-expressing T (CAR-T) cells induce robust antitumor responses in patients with hematologic malignancies. However, CAR-T cells exhibit only limited efficacy against solid tumors such as hepatocellular carcinoma (HCC), partially due to their limited expansion and persistence. CD8+ T cells, as key components of the adaptive immune response, play a central role in antitumor immunity. Aerobic glycolysis is the main metabolic feature of activated CD8+ T cells. In the tumor microenvironment, however, the uptake of large amounts of glucose by tumor cells and other immunosuppressive cells can impair the activation of T cells. Only when tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment have a glycolytic advantage might the effector function of T cells be activated. Glucose transporter type 1 (GLUT1) and acylglycerol kinase (AGK) can boost glycolytic metabolism and activate the effector function of CD8+ T cells, respectively. In this study, we generated GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK for the treatment of HCC. GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK specifically and effectively lysed GPC3-positive tumor cells in vitro in an antigen-dependent manner. Furthermore, GLUT1 or AGK overexpression protected CAR-T cells from apoptosis during repeated exposures to tumor cells. Compared with second-generation CAR-T cells, GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK exhibited greater CD8+ T-cell persistence in vivo and better antitumor effects in HCC allograft mouse models. Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

Host T Cell Dedifferentiation Effects Drive HIV-1 Latency Stability.

The development of therapies to eliminate the latent HIV-1 reservoir is hampered by our incomplete understanding of the biomolecular mechanism governing HIV-1 latency. To further complicate matters, recent single-cell RNA sequencing (scRNA-seq) studies reported extensive heterogeneity between latently HIV-1-infected primary T cells, implying that latent HIV-1 infection can persist in greatly differing host cell environments. We show here that transcriptomic heterogeneity is also found between latently infected T cell lines, which allowed us to study the underlying mechanisms of intercell heterogeneity at high signal resolution. Latently infected T cells exhibited a dedifferentiated phenotype, characterized by the loss of T cell-specific markers and gene regulation profiles reminiscent of hematopoietic stem cells (HSC). These changes had functional consequences. As reported for stem cells, latently HIV-1-infected T cells efficiently forced lentiviral superinfections into a latent state and favored glycolysis. As a result, metabolic reprogramming or cell redifferentiation destabilized latent infection. Guided by these findings, data mining of single-cell RNA-seq data of latently HIV-1-infected primary T cells from patients revealed the presence of similar dedifferentiation motifs. More than 20% of the highly detectable genes that were differentially regulated in latently infected cells were associated with hematopoietic lineage development (e.g., HUWE1, IRF4, PRDM1, BATF3, TOX, ID2, IKZF3, and CDK6) or were hematopoietic markers (SRGN; hematopoietic proteoglycan core protein). The data add to evidence that the biomolecular phenotype of latently HIV-1-infected cells differs from that of normal T cells and strategies to address their differential phenotype need to be considered in the design of therapeutic cure interventions. IMPORTANCE HIV-1 persists in a latent reservoir in memory CD4 T cells for the lifetime of a patient. Understanding the biomolecular mechanisms used by the host cells to suppress viral expression will provide essential insights required to develop curative therapeutic interventions. Unfortunately, our current understanding of these control mechanisms is still limited. By studying gene expression profiles, we demonstrated that latently HIV-1-infected T cells have a dedifferentiated T cell phenotype. Software-based data integration allowed the identification of drug targets that would redifferentiate viral host cells and, by extension, destabilize latent HIV-1 infection events. The importance of the presented data lies within the clear demonstration that HIV-1 latency is a host cell phenomenon. As such, therapeutic strategies must first restore proper host cell functionality to accomplish efficient HIV-1 reactivation.

Synergistic Adsorption and In Situ Catalytic Conversion of SO2 by Transformed Bimetal-Phenolic Functionalized Biomass.

SO2 removal is critical to flue gas purification. However, based on performance and cost, materials under development are hardly adequate substitutes for active carbon-based materials. Here, we engineered biomass-derived nanostructured carbon nanofibers integrated with highly dispersed bimetallic Ti/CoOx nanoparticles through the thermal transition of metal-phenolic functionalized industrial leather wastes for synergistic SO2 adsorption and in situ catalytic conversion. The generation of surface-SO32- and peroxide species (O22-) by Ti/CoOx achieved catalytic conversion of adsorbed SO2 into value-added liquid H2SO4, which can be discharged from porous nanofibers. This approach can also avoid the accumulation of the adsorbed SO2, thereby achieving high desulfurization activity and a long operating life over 6000 min, preceding current state-of-the-art active carbon-based desulfurization materials. Combined with the techno-economic and carbon footprint analysis from 36 areas in China, we demonstrated an economically viable and scalable solution for real-world SO2 removal on the industrial scale.

The Addition of an Ultra-Small Amount of Black Phosphorous Quantum Dots Endow Self-Healing Polyurethane with a Biomimetic Intelligent Response.

This study explores new applications of black phosphorus quantum dots (BPQDs) by adding them to self-healing material systems for the first time. Self-healing polyurethane with an ultra-small amount of BPQDs has biomimetic intelligent responsiveness and achieves balance between its mechanical and self-healing properties. By adding 0.0001 wt% BPQDs to self-healing polyurethane, the fracture strength of the material increases from 3.0 to 12.3 MPa, and the elongation at break also increases from 750% to 860%. Meanwhile, the self-healing efficiency remains at 98%. The addition of BPQDs significantly improves the deformation recovery ability of the composite materials and transforms the surface of self-healing polyurethane from hydrophilic to hydrophobic, making it suitable for applications in fields such as electronic skin and flexible wearable devices. This study provides a simple and feasible strategy for endowing self-healing materials with biomimetic intelligent responsiveness using a small amount of BPQDs.

A systematic review and meta-analysis of observational studies of the association between the use of incretin-based therapies and the risk of pancreatic cancer.

BACKGROUND: Some early reports in the medical literature have raised concern about a possible increased risk of pancreatic cancer associated with the use of two broad classes of incretin-based therapies, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 receptor agonists. This possibility has been somewhat mitigated by the null findings meta-analyses of randomized controlled trials, but the usefulness of their findings was hampered by serious shortcomings of lack of power and representativeness. These shortcomings can typically be addressed by observational studies, but observational studies on the topic have yielded conflicting findings. A systematic review and meta-analysis of observational studies was performed to qualitatively and quantitatively appraise the totality of evidence on the association between the use of incretin-based therapies and the risk of pancreatic cancer in routine clinical practice. METHODS: The PubMed, Web of Science, Embase, and Google Scholar databases were searched. The study quality was appraised using the ROBINS-I tool and based on the presence of pharmacoepidemiology biases. A random-effects model was used to estimate the summary relative risks with corresponding CIs. RESULTS: A total of 14 studies were included. The qualitative assessment revealed that all studies had inadequate follow-up (≤5 years), 12 studies were suspected to suffer from time-lag bias (due to inappropriate choice of comparator group) to varying extent, five studies included prevalent users, five studies did not implement exposure lag period, five studies had a serious risk of bias due to confounding, and one study had a time-window bias. The quantitative assessment showed no indication of an increased risk when all studies were pooled together (RR 1.04, 95% CI 0.87, 1.24) and when the analysis was restricted to the studies with the least bias (RR 0.77, 95% CI 0.51, 1.17). However, the pooled RRs were more frequently higher in the studies with less rigorous design and analysis. Specifically, a tendency toward an increased risk was observed in the studies with (RR 1.34, 95% CI 1.04, 1.72) or possibly with (RR 1.10, 95% CI 0.89, 1.36) time-lag bias, in the studies that did not apply (RR 1.23, 95% CI 0.93, 1.63) or with potentially inadequate exposure lag period of 6 months (RR 1.13, 95% CI 0.66, 1.94), in the studies that inappropriate comparator group of a combination of unspecified (RR 1.49, 95% CI 1.25, 1.78) or non-insulin (RR 1.15, 95% CI 0.93, 1.42) antidiabetic drugs, and in the studies with serious risk of bias due to confounding (RR 1.18, 95% CI 0.56, 2.49). CONCLUSIONS: In summary, the totality of evidence from observational studies does not support the claim that the use of incretin-based therapies is associated with an increased risk of pancreatic cancer in routine clinical practice. The increased risk of pancreatic cancer observed in observational studies reflects bias resulting from suboptimal methodological approaches, which need to be avoided by future studies.

Highly efficient U(VI) capture from nuclear wastewater by an easily synthesized lignin-derived biochar: Adsorption performance and mechanism.

The efficient recycling of uranium (U) by adsorbents remains challenging due to the strong interference from coexisting impurities, insufficient desorption efficiency, and weak irradiation instability. In this work, a novel lignin-derived biochar (AL/BC) with high surface area and abundant functional groups was developed through a green and simple pyrolysis process, and an adsorbent for U(VI) capture was used. The optimist AL/BC-600 exhibited ultrahigh adsorption capacity for U(VI) of 4007 mg/g, possessing a wide pH range of 1-11, and powerful anti-interference ability when coexisting with various common cations and anions. In addition, AL/BC-600 showed high tolerance even under strong irradiation at a dose of 350 kGy. Most importantly, after the tenth round of the adsorption-desorption cyclic utilization, the adsorption efficiency and desorption rate of AL/BC-600 were actually over 95% and 80%, respectively. Hence, this study provides a green and simple process for synthesizing a novel adsorbent for highly efficient U(VI) capture, not only paving a path for alleviating the increasingly serious energy crisis, but also facilitating the low-carbon and circular development of lignin.

Preoperative Nutritional Status of Infants with Non-Restricted Ventricular Septal Defect and Its Influence on Postoperative Recovery.

PURPOSE: This study described the preoperative nutritional status of infants with nonrestricted ventricular septal defects (VSDs) and evaluated its effect on postoperative recovery. METHODS: We retrospectively collected data from infants with nonrestricted VSD who received surgical treatment in our hospital from January 2020 to December 2021 and analyzed their preoperative nutritional status and postoperative recovery. RESULTS: Fifty (53.8%) patients were underweight (weight for age Z score (WAZ) ≤-1), and 31 (33.3%) patients were malnourished (WAZ ≤-2). The mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery of patients with WAZ ≤-2 were significantly longer than those of patients with WAZ >-2 (p < 0.05). The results of linear correlation analysis showed that age, WAZ and prealbumin were negatively correlated with mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery, respectively. Multiple linear regression analysis showed that mechanical ventilation time = 7.080 - 0.668 WAZ - 0.013 prealbumin - 0.618 age (R2: 0.729, F: 79.773, p: 0.001); duration of intensive care unit admission = 11.775 - 1.385 WAZ - 0.018 prealbumin - 0.102 age (R2: 0.714, F: 74.072, p: 0.001); and hospital stay time = 17.663 - 1.673 WAZ - 0.017 prealbumin - 1.07 age (R2: 0.711, F: 72.842, p: 0.001). CONCLUSION: The incidence of malnutrition in infants with nonrestricted VSD was very high, and malnutrition had a significant adverse effect on postoperative recovery. Malnutrition significantly prolonged mechanical ventilation time, duration of intensive care unit stay and hospital stay after surgery.

A cleaner leather chemical from feather waste for reducing ammonia-nitrogen pollution and improving biological treatment efficiency of tannery wastewater.

Feather waste is produced in millions of tons globally every year, resulting in a waste of biomass resources and even environmental pollution. A sustainable strategy for utilizing feather waste was proposed by preparing a clean deliming agent for ammonia-nitrogen (NH3-N) reduction in leather manufacture and biological treatment efficiency improvement of tannery wastewater. Briefly, chicken feather wastes were deeply hydrolyzed with sulfuric acid, and the optimized keratin hydrolysate (KHopt) that contained 53.6% crude protein and 41.2% amino acids, such as glutamic acid, serine, proline, leucine, phenylalanine, glycine, valine, and arginine, was obtained and used to delime limed cattle hides. The appropriate ratio of amino acids in KHopt gave KHopt a great pH-buffering capacity and maintained a stable float pH of approximately 9 throughout the deliming process. The isoelectric points of KHopt (3.8) and the limed hide (6.3) were both lower than the float pH, thereby bringing about an electrostatic repulsion between the KHopt and the hide surface, which is helpful for KHopt to penetrate and deswell the limed hide rapidly. Moreover, the KHopt deliming effectively removed calcium from the limed hide and achieved leather comparable to conventional leather for commercial applications. KHopt reduced the NH3-N concentrations of deliming effluent and tannery wastewater by 91.1% and 80.6%, respectively, compared with the conventional deliming agent (ammonium sulfate), and dramatically increased the biological treatment efficiency of tannery wastewater. The results showed that efficient and high-value use of feather waste was made by preparing KHopt for sustainable leather manufacturing.

[Impact of assisted reproductive technology on birth weight discordance in twins]. / è¾ åŠ©ç”Ÿæ®–æŠ€æœ¯å¯¹åŒèƒŽå‡ºç”Ÿä½“é‡ä¸ä¸€è‡´çš„å½±å“.

OBJECTIVES: To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). METHODS: A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. RESULTS: A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). CONCLUSIONS: ART is not associated with the risk of BWDT.

Effect of Dialdehyde Carboxymethyl Cellulose Cross-Linking on the Porous Structure of the Collagen Matrix.

Porous structures are essential for some collagen-based biomaterials and can be regulated by crosslinkers. Herein, dialdehyde carboxymethyl cellulose (DCMC) crosslinkers with similar size but different aldehyde group contents were prepared through periodate oxidation of sodium carboxymethyl cellulose with varying degrees of substitution (DS). They can penetrate into the hierarchy of fibril and form inter-molecular and intra-fibril cross-linking within the collagen matrix due to their nanoscale sizes and reactive aldehyde groups. The collagen matrices possessed higher porosity, significantly greater proportion of large pores (Φ > 10 µm), and shorter D-periodicity after cross-linking, showing greater potential for biomedical applications. In addition, the crosslinked collagen matrices showed satisfactory biocompatibility and biodegradation. The decreased DS of carboxymethyl cellulose, which led to the increased aldehyde content of corresponding DCMC, brought about an enhanced cross-linking degree, porosity, and proportion of large pores of the crosslinked collagen matrix. DCMC dosage of 6% was sufficient for cross-linking and pore formation. Excess DCMC would physically deposit in the matrix and decrease the porosity instead. Therefore, the desired pore properties of the collagen matrix could be obtained by regulating the structure of DCMC and thereby achieving the required functions of the biomaterial.

Polyethyleneimine/hydrated titanium oxide-functionalized fibrous adsorbent for removing cobalt: Adsorption performance and irradiation stability.

Radionuclides of 60Co often encountered in the fields of radiation therapy, medical preparation, and equipment sterilization, which have been considered fatal. Therefore, developing efficient and irradiation-stable adsorbents for the removal of 60Co in wastewater is urgently needed. An irradiation-stable fibrous adsorbent was fabricated through the surface functionalization of collagen fibers (CFs) by polyethyleneimine (PEI) and hydrated titanium oxide (TiO) (PEI-TiO-CFs). PEI-TiO-CFs, including their adsorption performance and irradiation stability, were systematically investigated. Results showed that PEI-TiO-CFs exhibit a maximum adsorption capacity of 0.5575 mmol g-1. In addition, the adsorption capacity of PEI-TiO-CFs only demonstrated a slight decrease in the selectivity investigation of Co2+ mixed with another coexisting ion, such as Na+, K+, and NO3-, Cl-. Furthermore, breakthrough point of PEI-TiO-CFs in column is high at 80 BV (bed volume) and the PEI-TiO-CF column can be mostly regenerated using 12 BV of Na2EDTA solution. Excellent irradiation stability of PEI-TiO-CFs was confirmed by the maintained morphology and adsorption capacity after irradiation at 350 kGy of 60Co γ-ray. Results indicated that PEI-TiO-CFs are an effective adsorbent for radioactive cobalt removal from aqueous solutions.

[Sex differences in clinical outcomes of extremely preterm infants/extremely low birth weight infants: a propensity score matching study]. / è¶ æ—©äº§å„¿/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ä¸´åºŠç»“å±€çš„æ€§åˆ«å·®å¼‚ï¼šä¸€é¡¹å€¾å‘æ€§è¯„åˆ†åŒ¹é ç ”ç©¶.

OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Bach2 Negatively Regulates T Follicular Helper Cell Differentiation and Is Critical for CD4+ T Cell Memory.

T follicular helper (Tfh) cells are essential for germinal center B cell responses. The molecular mechanism underlying the initial Tfh cell differentiation, however, is still incompletely understood. In this study, we show that in vivo, despite enhanced non-Tfh cell effector functions, the deletion of transcription factor Bach2 results in preferential Tfh cell differentiation. Mechanistically, the deletion of Bach2 leads to the induction of CXCR5 expression even before the upregulation of Ascl2. Subsequently, we have identified a novel regulatory element in the murine CXCR5 locus that negatively regulates CXCR5 promoter activities in a Bach2-dependent manner. Bach2 deficiency eventually results in a collapsed CD4+ T cell response with severely impaired CD4+ T cell memory, including Tfh cell memory. Our results demonstrate that Bach2 critically regulates Tfh cell differentiation and CD4+ T cell memory.

Irradiation-stable hydrous titanium oxide-immobilized collagen fibers for uranium removal from radioactive wastewater.

Developing efficient adsorbents with radiation stability for uranium removal from nuclear wastewater is greatly important for resource sustainability and environmental safety in manufacturing nuclear fuel. A novel adsorbent of hydrous titanium oxide-immobilized collagen fibers (HTO/CFs) with good radiation stability for UO22+ removal was developed. Results showed that the adsorption capacity of HTO/CFs for UO22+ was 1.379 mmol g-1 at 303 K and pH 5.0 when the initial concentration of UO22+ was 2.5 mmol L-1. Moreover, HTO/CFs showed high selectivity for U(VI) in bilateral mixed solution including UO22+ with another coexisting ion, such as Cl-, NO3-, Zn2+, and Mg2+. The adsorption behavior of UO22+ from radioactive wastewater on HTO/CF column was also investigated, and the breakthrough point was approximately 250 BV (bed volume). Notably, the HTO/CFs column can be rapidly regenerated by using only 4.0 BV of 0.1 mol L-1 HNO3 solution. The regenerated HTO/CFs column exhibited slight change in the breakthrough curve, suggesting its excellent reapplication ability. Furthermore, after irradiation under 60Co γ-ray at total doses of 10-350 kGy, HTO/CFs still preserved fibrous morphology and adsorption capacity, indicating significant radiation stability. These results demonstrate that HTO/CFs are industrial scalable adsorbents for the adsorptive recovery of uranium.

Ornithinibacillus caprae sp. nov., a moderate halophile isolated from the hides of a white goat.

A novel Gram-stain-positive, motile, moderate halophile, strain L9T, was isolated from hides of white goat in China. The isolate grew optimally at 30 °C, at pH 7 and with 5-10% (w/v) NaCl. The predominant menaquinone was MK-7, and the major cellular fatty acids were identified as iso-C15:0 and anteiso-C15:0. The peptidoglycan amino acid type was determined to be A4ß, containing L-ornithine and D-aspartic as diagnostic amino acids. The phospholipids were dominated by diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophospholipid and two unidentified phospholipids. Genome sequencing resulted in a genome size of 4.0 Mbp and a DNA G + C content of 35.9 mol%. Phylogenetic trees based on the 16S rRNA gene sequences showed the isolate to be closely related to Oceanobacillus limi H9BT (98.2% similarity) and Ornithinibacillus halophilus G8BT (97.5% similarity). The ANI and dDDH values between strain L9T and the closely related species were 69.8-76.1% and 13.0-20.5%, respectively. On the basis of the data presented, strain L9T represents a novel species of the genus Ornithinibacillus, for which the name Ornithinibacillus caprae sp. nov. is proposed. The type strain is L9T (= KCTC 43176T = CGMCC 1.17659T).

Halomonas pellis sp. nov., a moderately halophilic bacterium isolated from wetsalted hides.

A Gram-stain-negative, moderately halophilic strain, designated strain L5T, was isolated from wetsalted hides collected from Chengdu, south-west PR China. The cells were motile, facultative aerobic, short rod-shaped and non-endospore-forming. Growth of strain L5T occurred at pH 6-10 (optimum, pH 8), 10-45 °C (optimum, 30 °C) and in the presence of 1-17 % (w/v) NaCl (optimum, 10 %). Results of phylogenetic analyses based on 16S rRNA, gyrB and rpoD gene sequences and its genome revealed that strain L5T belonged to the genus Halomonas. Strain L5T was found to be most closely related to the type strains of Halomonas saliphila, Halomonas lactosivorans, Halomonas kenyensis, Halomonas daqingensis and Halomonas desiderata (98.8, 98.6, 98.3, 97.9 and 97.4 % 16S rRNA gene sequence similarity, respectively). The draft genome was approximately 4.2 Mb in size with a G+C content of 63.5 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization values among strain L5T and the selected Halomonas species were 83.3-88.9 % (ANIm), 71.1-87.3 % (ANIb) and 20.2-34.6 %, which are below the recommended cutoff values. Major fatty acids were C16 : 0, C16 : 1 ω7c, C18 : 1 ω7c and C19 : 0 cyclo ω8c and the predominant ubiquinone was Q-9, with minor ubiquinone Q-8 also present. The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, four unidentified aminophospholipids and three unidentified phospholipids. Based on the mentioned polyphasic taxonomic evidence, strain L5T represents a novel species within the genus Halomonas, for which Halomonas pellis sp. nov. is proposed. The type strain is L5T (=CGMCC 1.17335T=KCTC 72573T).

Foxp1 Negatively Regulates T Follicular Helper Cell Differentiation and Germinal Center Responses by Controlling Cell Migration and CTLA-4.

T follicular helper (Tfh) cells play an essential role in the formation of germinal centers (GC) and generation of high-affinity Abs. The homing of activated CD4+ T cells into B cell follicles and the involvement of key costimulatory and coinhibitory molecules are critical in controlling both the initiation and the magnitude of GC responses. Meanwhile, studies have shown that a high number of single clone B cells leads to intraclonal competition, which inhibits the generation of high-affinity Abs. Our previous work has shown that transcription factor Foxp1 is a critical negative regulator of Tfh cell differentiation. In this study, we report that the deletion of Foxp1 leads to a high proportion of activated CD4+ T cells homing into B cell follicles with faster kinetics, resulting in earlier GC formation. In addition, we show that Foxp1-deficient Tfh cells restore the generation of high-affinity Abs when cotransferred with high numbers of single clone B cells. We find that Foxp1 regulates the expression levels of cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) in activated CD4+ T cells and that Ctla4 is a direct Foxp1 target. Finally, we demonstrate that CTLA-4 expression on conventional CD4+ T cells plays a cell-intrinsic role in Tfh cell differentiation in vivo, and CTLA-4 blockade helps abolish the intraclonal competition of B cells in generating high-affinity Abs.