Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.

Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.

Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system.

Mycobacterium tuberculosis PtpA, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. Here we found that PtpA suppressed innate immunity dependent on pathways of the kinases Jnk and p38 and the transcription factor NF-κB by exploiting host ubiquitin. Binding of PtpA to ubiquitin via a region with no homology to human proteins activated it to dephosphorylate phosphorylated Jnk and p38, leading to suppression of innate immunity. Furthermore, the host adaptor TAB3 mediated NF-κB signaling by sensing ubiquitin chains, and PtpA blocked this process by competitively binding the ubiquitin-interacting domain of TAB3. Our findings reveal how pathogens subvert innate immunity by coopting host ubiquitin and suggest a potential tuberculosis treatment via targeting of ubiquitin-PtpA interfaces.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20flox mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca2+ content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes. CONCLUSIONS: These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.

A biomimetic eye with a hemispherical perovskite nanowire array retina.

Human eyes possess exceptional image-sensing characteristics such as an extremely wide field of view, high resolution and sensitivity with low aberration1. Biomimetic eyes with such characteristics are highly desirable, especially in robotics and visual prostheses. However, the spherical shape and the retina of the biological eye pose an enormous fabrication challenge for biomimetic devices2,3. Here we present an electrochemical eye with a hemispherical retina made of a high-density array of nanowires mimicking the photoreceptors on a human retina. The device design has a high degree of structural similarity to a human eye with the potential to achieve high imaging resolution when individual nanowires are electrically addressed. Additionally, we demonstrate the image-sensing function of our biomimetic device by reconstructing the optical patterns projected onto the device. This work may lead to biomimetic photosensing devices that could find use in a wide spectrum of technological applications.

Biosynthetic mechanisms of omega-3 polyunsaturated fatty acids in microalgae.

Marine microalgae are the primary producers of ω3 polyunsaturated fatty acids (PUFAs), such as octadecapentaenoic acid (OPA, 18:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) for food chains. However, the biosynthetic mechanisms of these PUFAs in the algae remain elusive. To study how these fatty acids are synthesized in microalgae, a series of radiolabeled precursors were used to trace the biosynthetic process of PUFAs in Emiliania huxleyi. Feeding the alga with 14C-labeled acetic acid in a time course showed that OPA was solely found in glycoglycerolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) synthesized plastidically by sequential desaturations while DHA was exclusively found in phospholipids synthesized extraplastidically. Feeding the alga with 14C-labeled α-linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) showed that DHA was synthesized extraplastidically from fed ALA and LA, but not from OA, implying that the aerobic pathway of DHA biosynthesis is incomplete with missing a Δ12 desaturation step. The in vitro enzymatic assays with 14C-labeled malonyl-CoA showed that DHA was synthesized from acetic acid by a PUFA synthase. These results provide the first and conclusive biochemistry evidence that OPA is synthesized by a plastidic aerobic pathway through sequential desaturations with the last step of Δ3 desaturation, while DHA is synthesized by an extraplastidic anaerobic pathway catalyzed by a PUFA synthase in the microalga.

Structural and functional analysis of plant ELO-like elongase for fatty acid elongation.

ELO-like elongase is a condensing enzyme elongating long chain fatty acids in eukaryotes. Eranthis hyemalis ELO-like elongase (EhELO1) is the first higher plant ELO-type elongase that is highly active in elongating a wide range of polyunsaturated fatty acids (PUFAs) and some monounsaturated fatty acids (MUFAs). This study attempted using domain swapping and site-directed mutagenesis of EhELO1 and EhELO2, a close homologue of EhELO1 but with no apparent elongase activity, to elucidate the structural determinants critical for catalytic activity and substrate specificity. Domain swapping analysis of the two showed that subdomain B in the C-terminal half of EhELO1 is essential for MUFA elongation while subdomain C in the C-terminal half of EhELO1 is essential for both PUFA and MUFA elongations, implying these regions are critical in defining the architecture of the substrate tunnel for substrate specificity. Site-directed mutagenesis showed that the glycine at position 220 in the subdomain C plays a key role in differentiating the function of the two elongases. In addition, valine at 161 and cysteine at 165 in subdomain A also play critical roles in defining the architecture of the deep substrate tunnel, thereby contributing significantly to the acceptance of, and interaction with primer substrates.

Construction of Stable 2D Cationic Breathing Ni-MOF for Cr(VI) Trapping and Electrochemical Sensing.

Pollution of surface water by heavy metal hexavalent chromium ions poses a serious threat to human health; herein, a two-dimensional (2D) cationic breathing Ni-MOF with free nitrate ions between the layers was designed and synthesized according to the characteristics of hexavalent chromium ions, {[Ni(L)2](NO3)2·5H2O}n (L = 1,3,5-tris[4-(imidazol-1-yl)phenyl]benzene). The flexible layer spacing of the 2D breathing Ni-MOF allows the exchange of NO3- by CrO42- without destroying the original structure. Electrostatic and hydrogen bonding interactions between CrO42- and Ni-MOF facilitate its exchange with NO3-. Moreover, CrO42- exhibits a higher binding energy with Ni-MOF compared to NO3-, and the hydrophobic channels of Ni-MOF favor CrO42- trapping due to its lower hydration energy. Consequently, Ni-MOF demonstrates both effective sorption and electrochemical sensing of Cr(VI), achieving a sensitivity of 2.091 µA µM-1 and a detection limit of 0.07 µM.

Copper-catalyzed tandem cyclization reaction of ethynylbenzoxazinones and thiols: facile construction of 2-thiomethylene indoles.

The first successful copper-catalyzed decarboxylative cyclization reaction of ethynylbenzoxazinones and thiols has been developed. A rarely studied α-addition process to a copper-allenylidene intermediate promoted this reaction. Using this protocol, a range of 2-thiomethylene indole compounds have been obtained. This methodology offers significant advantages including mild reaction conditions, cheap catalysts, good yields and broad substrate compatibility.

Perioperative Hypothermia in Elderly Patients During Pelvic Floor Reconstruction Surgery: An Observational Study.

INTRODUCTION AND HYPOTHESIS: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia. METHODS: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia. RESULTS: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828). CONCLUSIONS: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery.

Benefit finding in chronic kidney disease patients receiving hemodialysis: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.

0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period.

BACKGROUND: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. METHODS: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. RESULTS: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. CONCLUSIONS: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. CLINICAL TRIAL NUMBER AND REGISTRY URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022.

The effects and mechanisms of heat stress on mammalian oocyte and embryo development.

The sum of nonspecific physiological responses exhibited by mammals in response to the disruption of thermal balance caused by high-temperature environments is referred to as heat stress (HS). HS affects the normal development of mammalian oocyte and embryos and leads to significant economic losses. Therefore, it is of great importance to gain a deep understanding of the mechanisms underlying the effects of HS on oocyte and embryonic development and to explore strategies for mitigating or preventing its detrimental impacts in the livestock industry. This article provides an overview of the negative effects of HS on mammalian oocyte growth, granulosa cell maturation and function, and embryonic development. It summarizes the mechanisms by which HS affects embryonic development, including generation of reactive oxygen species (ROS), endocrine disruption, the heat shock system, mitochondrial autophagy, and molecular-level alterations. Furthermore, it discusses various measures to ameliorate the effects of HS, such as antioxidant use, enhancement of mitochondrial function, gene editing, cultivating varieties possessing heat-resistant genes, and optimizing the animals'rearing environment. This article serves as a valuable reference for better understanding the relationship between HS and mammalian embryonic development as well as for improving the development of mammalian embryos and economic benefits under HS conditions in livestock production.

Comparative analysis of different treatment strategies for septic spondylitis: a retrospective study of one hundred and twelve patients.

PURPOSE: To compare the clinical efficacy and prognosis differences between conservative treatment and surgical treatment in patients with non-serious neurologically intact pyogenic spondylitis (Nsi-Nsni-PS), and to provide theoretical reference for the clinical treatment of Nsi-Nsni-PS patients. METHODS: A retrospective analysis was conducted on 112 cases of Nsi-Nsni-PS patients treated in our hospital from June 2016 to June 2021. According to different treatment methods, they were divided into conservative treatment group (53 cases) and surgical treatment group (59 cases). The general data, laboratory tests, imaging examinations, length of hospital stay, duration of antibiotic use, VAS for pain before and after treatment, ODI, local kyphotic angle correction of diseased vertebrae, and recurrence rate were collected and analyzed in both groups. SPSS 26.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation, and independent sample t-test or rank sum test was used for comparison between groups, while variance analysis was used for intra-group comparison. Count data were expressed as number (%) and compared between groups using chi-square test or Fisher's exact test. Mann-Whitney U test was used to evaluate the changes in local kyphotic angle between the two groups. A p value < 0.05 was considered statistically significant. RESULTS: There were no significant differences in general data and imaging characteristics between the two groups (P > 0.05); there were no statistically significant differences in the positive culture rate of pathogens, length of hospital stay, duration of antibiotic use, treatment complications, WBC, CRP, ESR levels at admission and discharge, VAS and ODI at admission and last follow-up between the two groups (P > 0.05). The WBC and CRP levels of patients in the conservative group at discharge were lower than those in the surgical group (P < 0.05), and there was no significant difference in the decrease in inflammatory indicators (WBC, CRP, ESR) between the two groups (P > 0.05). By the last follow-up, the neurological function of patients in both groups had significantly improved compared to admission (P < 0.05), with 12 out of 15 ASIA grade D patients in the conservative group recovering to grade E, and 21 out of 25 grade D patients in the surgical group recovering to grade E, with no worsening of neurological function in either group. The differences in VAS and ODI scores at the last follow-up compared to before treatment were statistically significant in both groups (P < 0.05), and all patients regained normal activity. Compared with before treatment, the correction degree of local kyphotic angle in the surgical group at the last follow-up was 0.93 ± 4.94°, slightly higher than that in the conservative group (-0.83 ± 3.37°), and the difference was statistically significant(P < 0.05). CONCLUSIONS: During our follow-up, we found that both conservative and surgical treatments achieved satisfactory clinical outcomes in patients with Nsi-Nsni-PS. Compared to conservative treatment, surgical intervention did not demonstrate significant advantages in reducing hospitalization time and antibiotic usage duration, increasing pathogen culture positivity rate, lowering treatment complications, or controlling recurrence. However, surgical intervention showed superiority in correcting the local kyphotic angle of spinal lesions, albeit with relatively increased surgical trauma, risks, and treatment costs. At the last follow-up, the surgical group did not exhibit better long-term efficacy. Therefore, when formulating clinical treatment strategies for patients with Nsi-Nsni-PS, it may be preferable to prioritize conservative treatment, supplemented by the use of sensitive or empiric antibiotics for infection management, to improve patient prognosis.

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

Highly Efficient Electrosynthesis of Urea from CO2 and Nitrate by a Metal-Organic Framework with Dual Active Sites.

Electrosynthesis of urea from CO2 and NO3 - is a sustainable alternative to energy-intensive industrial processes. The main challenge hindering the progress of this technology lies in the development of advanced electrocatalysts that efficiently utilize abundant, low-cost CO2 and nitrogen sources to yield urea with both high Faradaic efficiency (FE) and current density. In this work, we designed and prepared a new two-dimensional metal-organic framework (MOF), namely PcNi-Fe-O, constructed by nickel-phthalocyanine (NiPc) ligands and square-planar FeO4 nodes, as the electrocatalyst for urea electrosynthesis. PcNi-Fe-O exhibits remarkable performance to yield urea at a high current density of 10.1 mA cm-2 with a high FE(urea) of 54.1 % in a neutral aqueous solution, surpassing those of most reported electrocatalysts. No obvious performance degradation was observed over 20 hours of continuous operation at the current density of 10.1 mA cm-2. By expanding the electrode area to 25 cm2 and operating for 8 hours, we obtained 0.164 g of high-purity urea, underscoring its potential for industrial applications. Mechanism study unveiled the enhanced performance might be ascribed to the synergistic interaction between NiPc and FeO4 sites. Specifically, NH3 produced at the FeO4 site can efficiently migrate and couple with the *NHCOOH intermediate adsorbed on the urea-producing site (NiPc). This synergistic effect results in a lower energy barrier for C-N bond formation than those of the reported catalysts with single active sites.

Glutamatergic and GABAergic neurons in the vLGN mediate the nociceptive effects of green and red light on neuropathic pain.

Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN, with red light increased more. In vLGN, green light causes a large increase in glutamatergic neurons, whereas red light causes a large increase in GABAergic neurons. Green light preconditioning increases the sensitivity of glutamatergic neurons to noxious stimuli in vLGN of PSL mice. Green light produces antinociception by activating glutamatergic neurons in vLGN, and red light promotes nociception by activating GABAergic neurons in vLGN. Together, these results demonstrate that different colors of light exert different pain modulation effects by regulating glutamatergic and GABAergic subpopulations in the vLGN. This may provide potential new therapeutic strategies and new therapeutic targets for the precise clinical treatment of neuropathic pain.

Warming in combination with increased precipitation mediate the sexual and clonal reproduction in the desert steppe dominant species Stipa breviflora.

BACKGROUND: Clonal plants can successfully adapt to various ecosystems. A trade-off between sexual and clonal reproduction is generally assumed in clonal plants, which may be influenced both by the characteristics of the plant itself and environmental conditions. Currently, it is unclear how climate change, and specifically warming and increased precipitation, might affect sexual and clonal reproduction in clonal plants. Therefore, this study aimed to investigate both the sexual and clonal reproduction responses of Stipa breviflora to warming and increased precipitation. A controlled experiment was conducted by inducing increases in precipitation (ambient condition, 25% and 50% increases) and warming (ambient temperature, 1.5 °C and 3.0 °C increases). RESULTS: Warming significantly influenced both the ratio of reproductive ramet shoot biomass to total shoot biomass, and the ratio of reproductive ramet number to total ramet number. Additionally, the ratio of reproductive ramet shoot biomass to total shoot biomass was also significantly affected by increased precipitation. Increased precipitation benefited sexual reproduction, while effects of warming on reproductive and/or vegetative ramets varied from negative to positive depending on precipitation conditions. There was no relationship between the number or shoot biomass of reproductive ramets and vegetative ramets. Reproductive ramets displayed greater sensitivity to climate change than vegetative ramets. CONCLUSIONS: The findings of our study suggest that there was no trade-off between sexual and clonal reproduction in S. breviflora. The combined impact of warming and increased precipitation promoted sexual reproduction but did not inhibit clonal reproduction. Clonal plants with the capacity for both sexual and clonal reproduction, may cope with climate change well via clonal reproduction, ensuring their survival.

New US capsule endoscopy for superficial and submucosal imaging of the esophagus: the first-in-human study.

BACKGROUND AND AIMS: EUS is essential in diagnosing and staging of esophageal subepithelial lesions and tumors. However, EUS is invasive, relies on highly trained endoscopists, and typically requires sedation. The newly developed US capsule endoscopy (USCE), which incorporates both white-light and US imaging modalities into a tethered capsule, is a minimally invasive method for obtaining superficial and submucosal information of the esophagus. This study aimed to assess the feasibility and safety of this USCE system. METHODS: Twenty participants were enrolled: 10 healthy volunteers and 10 patients with esophageal lesions indicated for EUS. Participants first underwent USCE and subsequently EUS within 48 hours. The primary outcome was the technical success rate of USCE. Secondary outcomes were safety, visualization of the esophagus, and comfort assessment. RESULTS: The technical success rate of USCE was 95% because 1 patient failed to swallow the capsule. No adverse events were observed. The esophagus was well visualized, and all lesions were detected under USCE optical mode in 19 participants. For healthy volunteers, the US images of normal esophageal walls were all characterized by differentiated 7-layer architecture under both USCE and EUS. For 9 patients, the features of esophageal lesions were recognized clearly under USCE, and presumptive diagnoses derived from USCE were all consistent with those from EUS. Most participants preferred USCE to EUS. CONCLUSIONS: The novel USCE is feasible and safe to observe the esophageal mucosa and acquire submucosal information, which has the potential to be widely used in the clinic. (Clinical trial registration number: NCT05054933.).

Small-sized versus standard magnetic capsule endoscopy in adults: a two-center, double-blinded randomized controlled trial.

BACKGROUND : Certain patients experience difficulty swallowing a video capsule endoscopy (VCE) device owing to its relatively large size. The newly developed small-sized magnetically controlled capsule endoscopy (MCE) device is the smallest VCE device ever reported. We aimed to evaluate the performance of the small-sized MCE device in terms of ingestion and examination efficacy. METHODS : Patients in two centers were prospectively enrolled and randomized to the small-sized or standard MCE groups. Differences in capsule ingestion difficulties, visualization of the gastrointestinal tract, and capsule transit times were compared. RESULTS : 96 patients were enrolled (48 in each group). In the small-sized MCE group, the mean (SD) difficulty score and time to swallow the capsule, and success rate for swallowing the capsule at the first attempt were 0.6 (1.0), 3.4 (1.3) seconds, and 89.6 %, which was significant better compared with the standard MCE group with 3.1 (1.7), 12.0 (14.3) seconds and 60.4 %, respectively (all P < 0.001). Visualization of the esophagus, stomach, and small bowel were comparable between the two groups. The small-sized MCE group had a significantly shorter gastric transit time (49.4 minutes vs. 66.2 minutes; P = 0.04) and longer small-bowel transit time (5.8 hours vs. 5.0 hours; P = 0.045). CONCLUSIONS : The small-sized MCE device is feasible and safe for gastrointestinal examination, alleviating difficulties in capsule ingestion, improving gastric emptying under magnetic control, and prolonging the small-bowel transit time.

Mycobacterium tuberculosis protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity.

Upon Mycobacterium tuberculosis (Mtb) infection, protein kinase G (PknG), a eukaryotic-type serine-threonine protein kinase (STPK), is secreted into host macrophages to promote intracellular survival of the pathogen. However, the mechanisms underlying this PknG-host interaction remain unclear. Here, we demonstrate that PknG serves both as a ubiquitin-activating enzyme (E1) and a ubiquitin ligase (E3) to trigger the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-ß-activated kinase 1 (TAK1), thereby inhibiting the activation of NF-κB signaling and host innate responses. PknG promotes the attachment of ubiquitin (Ub) to the ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), rather than the usual C86-Ub thiol-ester bond. PknG induces the discharge of Ub from UbcH7 by acting as an isopeptidase, before attaching Ub to its substrates. These results demonstrate that PknG acts as an unusual ubiquitinating enzyme to remove key components of the innate immunity system, thus providing a potential target for tuberculosis treatment.