Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell–Cell Communication Network Using CellChat

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell–cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell–cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell–cell interactome by assessing the gene expression of receptor–ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell–cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell–cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell–cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell–cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells

Association of social isolation with health status among community-dwelling Chinese older adults living with homecare services: a cross-sectional survey in Hong Kong

BackgroundDefined as having few social relationships or infrequent social contact with family, friends, and the community, social isolation is a public health crisis. We aimed to evaluate the prevalence of social isolation and explore the association between social isolation and health status among community-dwelling Chinese Older Adults living with homecare services.MethodsThis is a cross-sectional survey with a structured questionnaire conducted among older adults aged ≥60 in the Central Kowloon District of Hong Kong during 2017–2018. Social isolation was assessed by the Lubben Social Network Scale-6 and a score less than 12 was defined as socially isolated. Six aspects of health status including fall risk, cognitive function, depression, activities of daily living (ADL), instrumental activities of daily living (IADL), and functional mobility were measured by standardized instruments. Multi-criteria decision analysis (MCDA) was applied to estimate an index to represent the overall health status of the respondents. Multivariate logistic/linear regression models were applied to examine the associations between social isolation and health status after adjusting the sociodemographic characteristics.ResultsAmong the 1,616 participants included in this analysis, the mean age was 80.9 years, 66.3% were female and 41.4% were identified as socially isolated. Compared with the non-isolated group, the socially isolated group had higher proportions of males, divorced or unmarried, ever smoking and drinking, living alone, and living in public housing without religion. After adjusting for confounders, the odds ratios (OR) comparing the socially isolated vs. non-isolated groups were 2.52 (95%CI: 1.79, 3.56) for high fall risk, 1.51 (1.17, 1.94) for cognitive impairment, and 1.78 (1.31, 2.43) for depression. The socially isolated group increased the odds of abnormal ADL, IADL, and functional mobility by 105–150%, and decreased the overall health score by 5.30 (3.42, 7.18).ConclusionWe demonstrated the association of social isolation with poorer physical function and mental health and overall health status among the community-dwelling Chinese older adults living with homecare services. These findings provided new knowledge about the association of social isolation with both physical and mental function for daily living even for those receiving an integrated homecare service in the community. It implies that an unmet healthcare need existed when comparing the service scope of the current homecare services in the community. It also highlighted the need for targeted prevention and intervention initiatives among community-dwelling old adults to alleviate social isolation for better health and good functioning in the community

Single-step replacement of an unreactive C-H bond by a C-S bond using polysulfide as the direct sulfur source in anaerobic ergothioneine biosynthesis

Ergothioneine, a natural longevity vitamin and antioxidant, is a thiol-histidine derivative. Recently, two types of biosynthetic pathways were reported. In the aerobic ergothioneine biosynthesis, a non-heme iron enzyme incorporates a sulfoxide to an sp2 C-H bond in trimethyl-histidine (hercynine) through oxidation reactions. In contrast, in the anaerobic ergothioneine biosynthetic pathway in a green sulfur bacterium, Chlorobium limicola, a rhodanese domain containing protein (EanB) directly replaces this unreactive hercynine C-H bond with a C-S bond. Herein, we demonstrate that polysulfide (HSSnSR) is the direct sulfur-source in EanB-catalysis. After identifying EanB's substrates, X-ray crystallography of several intermediate states along with mass spectrometry results provide additional mechanistic details for this reaction. Further, quantum mechanics/molecular mechanics (QM/MM) calculations reveal that protonation of Nπ of hercynine by Tyr353 with the assistance of Thr414 is a key activation step for the hercynine sp2 C-H bond in this trans-sulfuration reaction.R01 GM106443 - NIGMS NIH HHS; R41 AT010878 - NCCIH NIH HHSAccepted manuscrip

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Study on asymptotic analytical solutions using HAM for strongly nonlinear vibrations of a restrained cantilever beam with an intermediate lumped mass

Presented herein is to establish the asymptotic analytical solutions for the fifth-order Duffing type temporal problem having strongly inertial and static nonlinearities. Such a problem corresponds to the strongly nonlinear vibrations of an elastically restrained beam with a lumped mass. Taking into consideration of the inextensibility condition and using an assumed single mode Lagrangian method, the single-degree-of-freedom ordinary differential equation can be derived from the governing equations of the beam model. Various parameters of the nonlinear unimodal temporal equation stand for different vibration modes of inextensible cantilever beam. By imposing the homotopy analysis method (HAM), we establish the asymptotic analytical approximations for solving the fifth-order nonlinear unimodal temporal problem. Within this research framework, both the frequencies and periodic solutions of the nonlinear unimodal temporal equation can be explicitly and analytically formulated. For verification, numerical comparisons are conducted between the results obtained by the homotopy analysis and numerical integration methods. Illustrative examples are selected to demonstrate the accuracy and correctness of this approach. Besides, the optimal HAM approach is introduced to accelerate the convergence of solutions

The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

Abstract Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders.</p

Relationship between patient experience and hospital readmission: system-level survey with deterministic data linkage method

Abstract Background Linkage of public healthcare data provides powerful resources for studying from a comprehensive view of quality of care than information for a single administrative database. It is believed that positive patient experiences reflect good quality of health care and may reduce patient readmission. This study aimed to determine the relationship between patient experience and hospital readmission at a system level by linking anonymous experience survey data with de-identified longitudinal hospital administrative admissions data. Methods Data were obtained by linking two datasets with anonymised individual-level records from seven largest-scale acute public hospitals over seven geographical clusters in Hong Kong. Selected records in the two datasets involving patient experience survey (PES) (2013 survey dataset) and healthcare utilization (admissions dataset) were used. Following data cleaning and standardization, a deterministic data linkage algorithm was used to identify pairs of records uniquely matched for a list of identifiers (10 selected variables) between two datasets. If patient’s record from the survey dataset matched with the hospitalization records in the admissions dataset, they were included in the subsequent analyses. Bivariate analyses and multivariable logistic regression models were performed to evaluate the associations between hospital readmission in the next calendar month and patient experience. Results The overall matching rate was 62.1% (1746/2811) for PES participants aged 45 or above from the survey dataset. The average score for overall inpatient experience was 8.10 (SD = 1.53). There was no significant difference between matched patients and unmatched patients in terms of their score for the perception of overall quality of care received during hospitalization (X 2 = 6.931, p-value = 0.14) and score for overall inpatient experience (X 2 = 7.853, p-value = 0.25). In the multivariable model, readmission through the outpatient department (planned admission) in the next calendar month was significantly associated with a higher score given to the overall quality of care received (adjusted OR = 1.54, 95%CI = 1.09–2.17), while such association was absent for readmission through Accident and Emergency department (adjusted OR = 0.75, 95%CI = 0.50–1.12). Conclusions This study demonstrated the feasibility of routine record linkage, with the limited intrusion of patients’ confidentiality, for evaluating health care quality. It also highlights the significant association between readmission through planned readmission and a higher score for overall quality of care received. A possible explanation might be the perceived better co-ordination between outpatient departments and inpatient service and the well-informed discharge plan given to this group of patients