Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

The impact of grandparenting on mental health among rural middle-aged and older adults in China: exploring the role of children's support.

Objectives: In the rural regions of China, characterized by a pronounced aging demographic and limited resources, a substantial proportion of middle-aged and older adults engage in grandparenting roles. Yet, the literature lacks consistent evidence regarding the effects of grandparenting on the mental health of this cohort. Accordingly, this study aimed to explore the impact of grandparenting on the mental health of rural middle-aged and older adults, as well as the underlying mechanisms. Methods: This analysis encompassed 10,881 middle-aged and older adults, utilizing data from the 2018 Harmonized China Health and Retirement Longitudinal Study (CHARLS). The mental health of participants was assessed using the Center for Epidemiological Studies Depression-10 (CESD-10) scale, while support from children was categorized into financial and emotional types. The study employed logistic and OLS regression models to identify the mediating role of child support and utilized the Karlson-Holm-Breen (KHB) method for decomposing this mediating effect. Results: The findings demonstrated that grandparenting had a significant negative impact on depression among rural middle-aged and older adults. Furthermore, children's support played a vital role in mediating this relationship, accounting for approximately one-third of the overall influence. Moreover, the decomposition analysis revealed that both emotional and economic support from adult children equally contributed to the declination of depression among rural middle-aged and older adults. Conclusion: Grandparenting significantly enhances mental well-being in rural middle-aged and older adults, with the support from adult children serving as a vital pathway for this positive impact. Both economic and emotional assistance from children hold equal importance in this dynamic. It underscores the necessity of fortifying the family support system to amplify the support provided by children, which in turn could significantly enhance the mental health of rural middle-aged and older adults.

Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling.

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

Increased Th17 cell frequency concomitant with decreased Foxp3+ Treg cell frequency in the peripheral circulation of patients with carotid artery plaques.

OBJECTIVE AND DESIGN: We investigated a possible imbalance between T helper (Th)17 and CD4+ CD25+ forkhead/winged helix transcription factor (Foxp3) T regulatory (Treg) cells in patients with carotid artery plaques. MATERIAL OR SUBJECTS: From November 2009 to September 2010, we enrolled 126 males and 104 females with mean age 68.24 ± 6.71 years. TREATMENT: Based on carotid artery sonography, the 230 subjects were categorized into three groups: plaque negative; stable plaques; and unstable plaques. METHODS: Th17 and Treg cell frequencies, relevant plasma cytokines (IL-17, IL-6, IL-23, and TNF-α), and RORγt mRNA levels were determined. RESULTS: Compared to plaque negative, Th17 cells, Th17-related cytokines (IL-17, IL-6, IL-23, and TNF-α), and RORγt mRNA levels were higher with stable plaques, and highest with unstable plaques. The opposite trend was found for Treg cells, Treg-related cytokines (IL-10 and TGF-ß1), and Foxp3 mRNA. Th17 cell frequencies were significantly negatively correlated with Treg cell frequencies. CONCLUSIONS: Our investigation demonstrated that there is a Th17/Treg functional imbalance in patients with unstable carotid atherosclerotic plaques. Th17 cells may promote atherogenesis, while Treg cells may have a protective role against atherosclerosis plaques. An imbalance of Th17/Treg cells may offer a new direction for the treatment of atherosclerosis.

Trends in water monomer adsorption and dissociation on flat insulating surfaces.

The interaction of water with solid surfaces is key to a wide variety of industrial and natural processes. However, the basic principles that dictate how stable and in which state (intact or dissociated) water will be on a given surface are not fully understood. Towards this end, we have used density functional theory to examine water monomer adsorption on the (001) surfaces of a broad range of alkaline earth oxides, alkaline earth sulfides, alkali fluorides, and alkali chlorides. Some interesting general conclusions are arrived at: (i) on all the surfaces considered only a few specific adsorption structures are favoured; (ii) water becomes more stable upon descending the oxide and fluoride series but does not vary much upon going down the chloride and sulfide series; (iii) water is stabilised both by an increase in the lattice constant, which facilitates hydrogen bonding to the substrate, and by the flexibility of the substrate. These are also factors that favour water dissociation. We hope that this study is of some value in better understanding the surface science of water in general, and in assisting in the interpretation and design of future experiments.

Proton transfer in adsorbed water dimers.

Density functional theory simulations of water on MgO(001) reveal rapid proton transfer within clusters of just two water molecules. Facile dissociation and recombination of the molecules within the dimers along with a concerted surface-mediated exchange of protons between water and hydroxyl molecules makes this possible. We suggest that surface-mediated proton transfer is in general likely to lead to proton transfer in interfacial water systems whenever the relative energies of intact and dissociated states of water are similar.

[Study on transvaginal hydrolaparoscopic pelvic adhesiolysis in the infertile women.].

OBJECTIVE: To investigate the safety and efficacy of transvaginal hydrolaparoscopic pelvic adhesiolysis (THLPA) treatment in the infertile women. METHODS: From May 2007 to Sep. 2008, 30 infertile patients underwent THLPA. The dye-test, hysteroscopy, and dye-test using catheterization of tubal ostium by hysteroscopy were performed at the same time. Pelvic adhesions were scored according to the revised American Fertility Society classification of endometriosis (1985). The adhesions were graded as mild (score 1-9), moderate (10-19), and severe (>/= 20). Twenty-four cases were in mild adhesions, 5 moderate adhesions, and 1 severe adhesion. The duration of the operation and discharge, pelvic adhesions score, tubal patency, complications, and pregnancy rate were investigated. RESULTS: (1) THPLA: the majority of pelvic adhesions in all patients were successfully performed adhesiolysis. Only a little filmy adhesions of proximal peritube of 7 tubes and proper ligament of 5 ovaries and cohesive adhesions of 4 ovaries did not underwent surgical lysis. (2) Tubal patency: 35 tubes were of proximal occlusion by dye-test, of which 21 (60%, 21/35) were unobstructed and 4 (11%, 4/35) were partly unobstructed after the dye-test using catheterization of the tubal ostium by hysteroscopy. (3) The duration of operation: the overall operative time were (32 +/- 6) minutes in mild adhesion, (52 +/- 6) minutes in moderate adhesion, and 83 minutes in severe adhesion. Of which the time of THLPA were (11 +/- 5) minutes in mild adhesion, (35 +/- 7) minutes in moderate adhesion, and 62 minutes in severe adhesion, respectively. (4) The duration of discharge: the postoperative discharge time was 120 - 175 minutes. No complications occurred. (5) The rate of pregnancy: in the (15.8 +/- 4.3) months' follow-up, the rate of pregnancy was 45% (13/29), which one patient lost follow-up. CONCLUSIONS: THLPA is safe, efficacious and not being hospitalized management. When compared with laparoscopy, it is simpler, more economic, and less minimally invasive approach. The appropriate indication of THLPA is to treat filmy, especially mild pelvic adhesions. It could partly avoid transabdominal operative laparoscopy for the infertile women.

Recombinant canine adenovirus type 2 expressing rabbit hemorrhagic disease virus VP60 protein provided protection against RHD in rabbits.

Rabbit hemorrhagic disease virus (RHDV) is responsible for rabbit hemorrhagic disease (RHD), which is an acute, lethal and highly contagious disease in both wild and domestic rabbits. Although current vaccines are highly effective for controlling RHD, they are derived from infected rabbit livers and their use is thus associated with safety and animal-welfare concerns. In this study, we generated a recombinant lentogenic canine adenovirus type 2 (CAV2) vector expressing the RHDV vp60 gene, named rCAV2-VP60. rCAV2-VP60 expressed VP60 protein in Madin-Darby canine kidney cells as demonstrated by western blot and immunofluorescence assay. Polymerase chain reaction confirmed that the vp60 gene was successfully inserted into rCAV2-VP60 and was still detectable after 20 passages, indicating its stable genetic character. We evaluated the feasibility of rCAV2-VP60 as a live-virus-vectored RHD vaccine in rabbits. rCAV2-VP60 significantly induced specific antibodies to RHDV and provided effective protection against RHDV lethal challenge. These results suggest that rCAV2 expressing RHDV VP60 could be a safe and efficient candidate vaccine against RHDV in rabbits.

Toward Accurate Adsorption Energetics on Clay Surfaces.

Clay minerals are ubiquitous in nature, and the manner in which they interact with their surroundings has important industrial and environmental implications. Consequently, a molecular-level understanding of the adsorption of molecules on clay surfaces is crucial. In this regard computer simulations play an important role, yet the accuracy of widely used empirical force fields (FF) and density functional theory (DFT) exchange-correlation functionals is often unclear in adsorption systems dominated by weak interactions. Herein we present results from quantum Monte Carlo (QMC) for water and methanol adsorption on the prototypical clay kaolinite. To the best of our knowledge, this is the first time QMC has been used to investigate adsorption at a complex, natural surface such as a clay. As well as being valuable in their own right, the QMC benchmarks obtained provide reference data against which the performance of cheaper DFT methods can be tested. Indeed using various DFT exchange-correlation functionals yields a very broad range of adsorption energies, and it is unclear a priori which evaluation is better. QMC reveals that in the systems considered here it is essential to account for van der Waals (vdW) dispersion forces since this alters both the absolute and relative adsorption energies of water and methanol. We show, via FF simulations, that incorrect relative energies can lead to significant changes in the interfacial densities of water and methanol solutions at the kaolinite interface. Despite the clear improvements offered by the vdW-corrected and the vdW-inclusive functionals, absolute adsorption energies are often overestimated, suggesting that the treatment of vdW forces in DFT is not yet a solved problem.

[Application of fertiloscopy in infertile women].

OBJECTIVE: To investigate the advantages of fertiloscopy in the examination and therapy of infertile women. METHODS: One hundred and fifteen infertile patients underwent fertiloscopy including transvaginal hydrolaparoscopy (THL), conventional dye-test, hysteroscopy, and dye-test using catheterization of the tubal ostium by hysteroscopy from May 2003 to Mar 2005. Access to the pouch of Douglas was achieved in 110 patients (95.7%). The primary infertile patients (primary group) and secondary infertile patients (secondary group) included respectively 49 and 61 cases. The patients of tubal occlusion in two groups were respectively 21 and 22 cases preoperatively. The fallopian tube patency, pelvic adhesions, complete evaluation (all pelvic organs seen) or not, and intra- and postoperative complications were observed. RESULTS: There was no significant difference in the percentage of uni- and bilateral tubal patency cases between two groups postoperatively (69.4%, 34/49 vs 68.9%, 42/61) (P > 0.05). Of the cases that were bilateral tubal occlusion in both groups preoperatively, the uni- and bilateral tubal patency cases accounted for respectively 47.6% (10/21) and 50.0% (11/22) (P > 0.05) postoperatively. There was no significant difference in the percentage of pelvic adhesions cases between two groups (42.9%, 21/49 vs 60.7%, 37/61; P > 0.05). The overall complete evaluation rate of pelvic organs was 69.1% (76/110), the rates of both groups were respectively 77.6% (38/49) and 62.3% (38/61, P > 0.05). The rate of additional transabdominal operative laparoscopy was 18.2% (20/110) after fertiloscopy, of which, the rate of primary group was only 8.2% (4/49), much less than that of secondary group (26.2%, 16/61; P < 0.05). Seventeen women underwent transabdominal operative minilaparoscopy after fertiloscopy. No complications including pelvic organ injury, rectum perforation, intra- and postoperative bleeding, and postoperative pelvic inflammation occurred. CONCLUSIONS: THL is simple, convenient, and complication-free for the infertile women. Fertiloscopy could be used as a first-line and one-stop procedure in the pelvic assessment of infertile women without clinical or ultrasound evidence of pelvic disease instead of transabdominal laparoscopy. Transabdominal laparoscopy should be only used as a complementary procedure after fertiloscopy.

[Study on combined transvaginal hydrolaparoscopy and hysteroscopy in patients with infertility].

OBJECTIVE: To evaluate the advantages of combined transvaginal hydrolaparoscopy (THL) and hysteroscopy in patients with infertility. METHODS: Twenty-three primary infertile patients (primary group) and 23 secondary infertile patients (secondary group) were received THL (using a 3-mm scope with a 0 degrees lens) and hysteroscopy. The fallopian tube patency, pelvic pathology, operative time, discharge time, healing time of vaginal wound, success rate of insertion into the pouch of Douglas and intra- and postoperative complications were observed. RESULTS: Primary group had more tube patency cases (P < 0.05) and fewer pelvic adhesion cases (P < 0.05) when compared with secondary group. Only 15.2% patients needed conventional laparoscopy postoperatively. The time of THL, overall time of operation, discharge time, and healing time of vaginal wound were respectively (10.5 +/- 1.7) min, (32.2 +/- 4.6) min, (87.3 +/- 12.5) min, and (4.5 +/- 0.5) days. No complications occurred. CONCLUSIONS: THL is accurate, minimally invasive, safe, economical, and does not require hospitalization. It could serve as a first-line procedure in early stages of infertility investigation when combined with hysteroscopy.

DFT-derived reactive potentials for the simulation of activated processes: the case of CdTe and CdTe:S.

We introduce a new ab initio derived reactive potential for the simulation of CdTe within density functional theory (DFT) and apply it to calculate both static and dynamical properties of a number of systems (bulk solid, defective structures, liquid, surfaces) at finite temperature. In particular, we also consider cases with low sulfur concentration (CdTe:S). The analysis of DFT and classical molecular dynamics (MD) simulations performed with the same protocol leads to stringent performance tests and to a detailed comparison of the two schemes. Metadynamics techniques are used to empower both Car-Parrinello and classical molecular dynamics for the simulation of activated processes. For the latter, we consider surface reconstruction and sulfur diffusion in the bulk. The same procedures are applied using previously proposed force fields for CdTe and CdTeS materials, thus allowing for a detailed comparison of the various schemes.

Atomistic structure of cobalt-phosphate nanoparticles for catalytic water oxidation.

Solar-driven water splitting is a key photochemical reaction that underpins the feasible and sustainable production of solar fuels. An amorphous cobalt-phosphate catalyst (Co-Pi) based on earth-abundant elements has been recently reported to efficiently promote water oxidation to protons and dioxygen, a main bottleneck for the overall process. The structure of this material remains largely unknown. We here exploit ab initio and classical atomistic simulations combined with metadynamics to build a realistic and statistically meaningful model of Co-Pi nanoparticles. We demonstrate the emergence and stability of molecular-size ordered crystallites in nanoparticles initially formed by a disordered Co-O network and phosphate groups. The stable crystallites consist of bis-oxo-bridged Co centers that assemble into layered structures (edge-sharing CoO(6) octahedra) as well as in corner- and face-sharing cubane units. These layered and cubane motifs coexist in the crystallites, which always incorporate disordered phosphate groups at the edges. Our computational nanoparticles, although limited in size to ~1 nm, can contain more than one crystallite and incorporate up to 18 Co centers in the cubane/layered structures. The crystallites are structurally stable up to high temperatures. We simulate the extended X-ray absorption fine structure (EXAFS) of our nanoparticles. Those containing several complete and incomplete cubane motifs-which are believed to be essential for the catalytic activity-display a very good agreement with the experimental EXAFS spectra of Co-Pi grains. We propose that the crystallites in our nanoparticles are reliable structural models of the Co-Pi catalyst surface. They will be useful to reveal the origin of the catalytic efficiency of these novel water-oxidation catalysts.