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Introduction Ankle pump exercise (APE) is an effective method to prevent deep vein thrombosis (DVT) in the lower extremities. However, traditional APE at a frequency of 3 times/min applied in the clinic lacked high compliance, and individuals were found to prefer an APE of 30 times/min. This study aimed to compare the effects of APEs with the above two different frequencies on the venous hemodynamics and fatigue of lower extremities. Methods The study applied a randomized cross-over design, and 307 healthy adults were randomly assigned into two groups, whose left feet performed 5 minutes of traditional APE (3 times/min, after 10 minutes of rest) and 5 minutes of selected APE (30 times/min, after 10 minutes of rest) in different orders. The diameters and blood flow velocities of the external iliac vein, femoral vein, and popliteal vein of the left extremities were recorded with the color doppler ultrasound when participants were at rest and after 5 minutes of traditional or selected APE. The fatigue of lower extremities was assessed with the Rating of Perceived Exertion (RPE) after the participants performed 5 minutes of different APEs. Results After both traditional APE and selected APE, the diameters and blood flow (peak systolic) velocities of the external iliac vein, femoral vein, and popliteal vein increased significantly in the participants (P.05). However, participants reported that traditional APE caused higher fatigue, and 252 (82.1%) participants preferred APE at 30 times/min. Conclusion Both traditional and selected APE could increase venous blood flow in the lower extremity. Despite the equivalent effects, the selected APE of 30 times/min may cause less fatigue than the traditional one of 3 times/min.

Critical gaps exist in our knowledge on how best to provide quality person-centered care to long-term care (LTC) home residents which is closely tied to not knowing what the ideal staff is complement in the home. A survey was created on staffing in LTC homes before and during the COVID-19 pandemic to determine how the staff complement changed. Perspectives were garnered from researchers, clinicians, and policy experts in eight countries and the data provides a first approximation of staffing before and during the pandemic. Five broad categories of staff working in LTC homes were as follows: (1) those responsible for personal and support care, (2) nursing care, (3) medical care, (4) rehabilitation and recreational care, and (5) others. There is limited availability of data related to measuring staff complement in the home and those with similar roles had different titles making it difficult to compare between countries. Nevertheless, the survey results highlight that some categories of staff were either absent or deemed non-essential during the pandemic. We require standardized high-quality workforce data to design better decision-making tools for staffing and planning, which are in line with the complex care needs of the residents and prevent precarious work conditions for staff.

Background A high tendency of intention to leave has been noted for nurses in China. The nursing profession is currently unstable. Methods A sample of 51406 nurses from 311 hospitals in China who completed the self-administered questionnaire online was recruited via the China Nursing Association by email and phone using a simple random sampling method. The recruitment occurred between July 2016 and July 2017. Results The majority of the nurses had working experience ≤20 years and had to work on night shifts. A high percentage of nurses (71.8%) had insomnia, followed by 37.0% who developed varicose veins and 40.9% who experienced musculoskeletal-related disorders. The proportions of the nurses who developed gastrointestinal and urinary system diseases were 56.0% and 18.2%, respectively. Nearly half of the nurses did not have a clear goal for their future career development and intended to leave. Nurses with long working hours each week were positively associated with the development of occupational diseases. The prevalence of occupational diseases was independently associated with career development. Conclusions A high prevalence of occupational diseases was noted among nurses in China. The data indicated that 50% of the nurses were vague regarding their career planning. The data suggest that managers need to pay more attention and to prevent this problem. Appropriate interventions should also be provided.

Depression in older population is more common now. Due to increasing numbers of older patients in hospitals, nurses have more opportunities to care for these patients. Therefore, nurses should have correct knowledge of late-life depression and more favorable attitudes about depression. The study aimed to understand hospital nurses’ knowledge level of late-life depression and attitudes about depression. A cross-sectional research design was used. A convenience sample of 307 nurses from 3 hospitals in Taiwan was recruited. Nurses scored 55.15% in the Late-Life Depression Quiz. The average score of the Revised Depression Attitude Questionnaire was 71.76 (SD = 6.13). The study also found that hospital nurses had more favorable attitudes about depression when their late-life depression knowledge was higher; their interest level in providing care for older patients with depression was greater; they had ever taken care of older patients with depressive symptoms or depression; they had never received in-service training on depression in the past year; and they had ever attended lectures about depression in school. Hospital nurses’ knowledge about late-life depression was limited, and they had neutral to slightly favorable attitudes about depression in Taiwan. It is suggested to carefully examine and evaluate in-service training related to depression for nurses in hospitals. In addition, developing appropriate interventions to increase hospital nurses’ knowledge level of late-life depression and attitudes toward depression is recommended.

Prostate cancer ranks second among male cancers in the United States in terms of death rate. Robot-assisted surgery (RAS) is now offered as the standard surgical procedure performed for radical prostatectomy. Urinary incontinence and erectile dysfunction were common complications after RAS prostatectomy. Patients felt ill-prepared after surgery, resulting in negative impacts on their quality of life. Pelvic floor muscle exercise is prioritized for patients with mild-to-moderate incontinence. The purpose of this study was to examine the effects of using resistance band pelvic floor muscle exercise for patients after RAS prostatectomy. A preexperimental single-group study was conducted for this study. A total of 43 patients completed the program. Urinary incontinence scale, Incontinence Impact Questionnaire, and Hospital Anxiety and Depression Scale were assessed at 0.5 months, 1 month, 2 months, and 3 months after urinary catheter removal. The results revealed that urinary incontinence, life impact, and depression and anxiety improved significantly as time went on. This study suggests that using simple and easy-to-learn resistance band pelvic floor muscle exercise program at home can benefit patients financially and reduce travel time.

Background: With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally., Methods: We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990-2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age‑period‑cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature., Results: In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14-4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019., Conclusion: There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations., (© 2024. The Author(s).)

Cobalt has the highest Curie temperature ( T c ) among the elemental ferromagnetic metals and has a hexagonal close-packed (HCP) structure at room temperature. In this study, HCP Co was thinned to the thickness of several ( n ) unit cells along the c -axis and then passivated by halogen atoms, thus being named Co 2 n X 2 (X = F, Cl, Br and I). For Co 2 X 2 and Co 3 X 2 , all of them are not only kinetically but also thermodynamically stable from the viewpoint of the phonon spectra and molecular dynamics. Similar to HCP Co, two-dimensional (2D) Co 2 F 2 , Co 2 Cl 2 and Co 3 X 2 (X = Cl, Br and I) are still ferromagnetic metals within the Stoner model but Co 2 X 2 (X = Br and I) is a ferromagnetic half-metal with the coexistence of the metallic behavior for one spin and the insulating behavior for the other spin. Taking into account the spin-orbital coupling (SOC), the easy-magnetization axis is within the plane where the magnetization is isotropic, making it look like a 2D XY magnet. Applying a critical biaxial strain could lead to an easy-magnetization axis changing from the in-plane to the out-of-plane direction. Finally, we use classical Monte Carlo simulations to estimate the Curie temperature ( T c ) which is as high as 957 and 510 K for Co 2 F 2 and Co 2 Cl 2 , respectively, because of the strong direct exchange interaction. Different from being obtained by mechanical or liquid exfoliation from van der Waals layered structures, our study opens up new possibilities to search for novel 2D ferromagnets from the elemental ferromagnets and provides opportunities for realizing realistic ultra-thin spintronic devices.

Purpose: Parents of children with cancer are exposed to risks of developing post-traumatic stress disorder (PTSD) symptoms, but few studies have explored PTSD symptoms of Chinese parents of children with acute lymphoblastic leukemia (ALL). Our study aimed to examine the association between social support and PTSD symptoms and to examine the mediating effect of positive expectations in this relationship among parents of children with ALL., Methods: A cross-sectional study was conducted of consecutive parents of children with ALL in the Shengjing Hospital of China Medical University. A total of 177 parents eligible for this study completed questionnaires on PTSD symptoms, perceived social support, optimism and general self-efficacy anonymously. Asymptotic and resampling strategies were used to examine how positive expectations mediated the association between perceived social support and PTSD symptoms., Results: Mean score of PTSD symptoms was 37.64 ± 14.44; 29.4% of the sample scored 44 and above, 19.8% scored 50 and above. After adjusting for covariates, perceived social support was negatively associated with the total score of PTSD symptoms (β = -0.209, p < 0.01). Positive expectations were found to mediate the relationship between perceived social support and PTSD symptoms, especially for the symptoms of avoidance and hyperarousal., Conclusions: Optimism and general self-efficacy fully mediated the association between perceived social support and PTSD symptoms. Therefore, social support and positive expectations should be included in PTSD preventions and treatments targeting Chinese parents of children with ALL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Dysphagia, a serious symptom of oral cancer, is also the most common. Further, patients who are more uncertain regarding their illness tend to catastrophize, which may affect their rehabilitation and long-term survival rate. Considering this relationship, this study aimed to investigate the occurrence of dysphagia in Chinese patients with oral cancer and explore the correlation between catastrophic cognition, illness uncertainty, and dysphagia., Methods: Applying a cross-sectional design, convenience sampling was used to recruit 180 patients with oral cancer. Advanced statistical methods were employed to analyze the mediating effects of catastrophic cognition on illness uncertainty and dysphagia., Results: Chinese patients with oral cancer had a mean dysphagia score of 52.88 ± 10.95. Catastrophic cognition and illness uncertainty in patients with oral cancer were significantly positively correlated (r = 0.447, P < 0.001). There was a significant negative correlation between dysphagia score and catastrophic cognition (r = -0.385, P < 0.001), and between dysphagia and illness uncertainty (r = -0.522, P < 0.001). Bootstrapping results indicated that the mediating effect of catastrophic cognition between illness uncertainty and dysphagia was -0.07 (95% CI: [-0.15, -0.03]) and significant, and the mediation effect accounted for 15.6% of the total effect., Conclusions: Chinese patients with oral cancer have poor swallowing function. Results suggest that catastrophic cognition partially mediated the relationship between illness uncertainty and dysphagia in patients with oral cancer. Medical staff can improve patients' swallowing function by reducing the level of catastrophic cognition via decreasing the level of illness uncertainty., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coherent interconversion between microwave and optical frequencies can serve as both classical and quantum interfaces for computing, communication, and sensing. Here, we present a compact microwave-optical transducer based on monolithic integration of piezoelectric actuators on silicon nitride photonic circuits. Such an actuator couples microwave signals to a high-overtone bulk acoustic resonator defined by the silica cladding of the optical waveguide core, suspended to enhance electromechanical and optomechanical couplings. At room temperature, this triply resonant piezo-optomechanical transducer achieves an off-chip photon number conversion efficiency of 1.6 × 10 -5 over a bandwidth of 25 MHz at an input pump power of 21 dBm. The approach is scalable in manufacturing and does not rely on superconducting resonators. As the transduction process is bidirectional, we further demonstrate the synthesis of microwave pulses from a purely optical input. Capable of leveraging multiple acoustic modes for transduction, this platform offers prospects for frequency-multiplexed qubit interconnects and microwave photonics at large., (© 2024. The Author(s).)

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti 6 O 6 (O i Pr) 8 (TTFTC)(phen) 2 ] 2 ( 1 , where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti 6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1 , in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity ( q ex ) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1 .

Considering the different fouling characteristics between model foulants and organic components in real reclaimed water, it is of great importance to identify the critical foulants responsible for membrane fouling. This study identified and isolated the fraction with molecular weight (MW) > 100 kDa as the critical foulant in secondary effluent by MW cut-off membrane of 100 kDa with high efficiency. This fraction accounted for 92.2% membrane fouling of raw water, including 28.7%, 29.7% and 33.8% fouling contribution by subfractions with MW between 100-300, 300-500 and > 500 kDa. Specifically, the critical fraction with MW > 100 kDa were mainly distributed in two parts: < 0.22 μm and > 0.45 μm, corresponding to 41.9% and 56.9% fouling contribution of this fraction. Furthermore, both total organic carbon (TOC) and fouling potential of fraction with MW > 100 kDa were monitored, presenting about threefold increase from September to January in next year. Membrane fouling contribution of this critical fraction in raw secondary effluent were mainly distributed in 85∼95% throughout the 5 months, demonstrating its predominant fouling propensity. Moreover, the TOC concentration of fraction with MW > 100 kDa presented distinct positive correlation with the fouling potential of raw secondary effluent (R 2  = 0.947), which was promising to be a surrogate for predicting membrane fouling in practical application., Competing Interests: Declaration of competing interest The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In low and medium income countries (LMIC) drinking water sources (wells and boreholes) often contain a high number of pathogenic microorganisms, that can pose significant human and environmental health risks. In this study, a quantitative microbial risk assessment approach based on existing literature was conducted to evaluate and compare the quantitative health risks associated with different age groups using various drinking water supply systems. Results showed that both community-supply and self-supply modes exhibit similar levels of risk. However, the self-supply water source consistently showed higher risks compared to the community-supply one. Borehole water was found to be a more suitable option than well water, consistently showing between 5 and 8 lower health risks for E. coli and fecal coliform levels, respectively. The sensitivity analysis further showed the importance of prioritizing the reduction of E. coli concentration in well water and fecal coliform concentration in borehole water. This study offers a fresh perception on quantifying the impact of exposure concentration and age groups, shedding light on how they affect environmental health risks. These findings provide valuable insights for stakeholders involved in the management and protection of water sources., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The purpose of this study was to measure the incidence of parastomal hernia (PH) after radical cystectomy and ileal conduit. Secondary aims were the identification of risk factors for PH and to compare the health-related quality of life (QOL) between patients with and without PH., Design: Retrospective review of medical records combined with cross-sectional administration of the QOL instrument and telephone follow-up., Subjects and Setting: The study sample comprised 219 patients who underwent radical cystectomy and ileal conduit for urothelial cancer between February 2014 and December 2018. The study setting was Peking University First Hospital (Beijing, China)., Methods: Demographic and pertinent clinical data, including development of PH, were gathered via the retrospective review of medical records. Participants were also asked to complete the traditional Chinese language version of the City of Hope Quality of Life-Ostomy Questionnaire (C-COH). Multiple linear regression analysis was used to identify the effect of PH on C-COH scores. Logistic regression analysis was used to identify risk factors for PH development., Results: At a median follow-up of 34 months (IQR = 21-48), 43 of 219 (19.63%) patients had developed a PH. A body mass index (BMI) indicating overweight (OR = 3.548; 95% CI, 1.562-8.061; P = .002), a prior history of hernia (OR = 5.147; 95% CI, 1.195-22.159; P = .028), and chronic high abdominal pressure postdischarge (CHAP-pd) (OR = 3.197; 95% CI, 1.445-7.075; P = .004) were predictors of PH after operation. There was no significant difference between C-COH scores of patients with or without PH. No significant differences were found when participants with PH were compared to those without PH on 4 factors of the C-COH: physical scores (β= .347, P = .110), psychological scores (β= .316, P = .070), spiritual scores (β=-.125, P = .714), and social scores (β= .054, P = .833)., Conclusion: Parastomal hernia is prevalent in patients undergoing radical cystectomy and ileal conduit urinary diversion. Overweight, hernia history, and CHAP-pd were predictors of PH development. No significant differences in QOL were found when patients with PH were compared to those without PH., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the Wound, Ostomy and Continence Nurses Society.)

The short de Broglie wavelength and strong interaction empower free electrons to probe structures and excitations in materials and biomolecules. Recently, electron-photon interactions have enabled new optical manipulation schemes for electron beams. In this work, we demonstrate the interaction of electrons with nonlinear optical states inside a photonic chip-based microresonator. Optical parametric processes give rise to spatiotemporal pattern formation corresponding to coherent or incoherent optical frequency combs. We couple such "microcombs" to electron beams, demonstrate their fingerprints in the electron spectra, and achieve ultrafast temporal gating of the electron beam. Our work demonstrates the ability to access solitons inside an electron microscope and extends the use of microcombs to spatiotemporal control of electrons for imaging and spectroscopy.

Objective: The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation., Methods: This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors., Results: Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level., Conclusion: The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources., (© 2023. The Author(s).)

Abstract: As the COVID-19 pandemic spread across the world, immunocompromised individuals such as people with HIV (PWH) may have faced a disproportionate impact on their health and HIV outcomes, both from COVID-19 and from the strategies enacted to contain it. Based on the SPIRIT guidelines, we describe the protocol for an international multisite observational study being conducted by The International Nursing Network for HIV Research, with the Coordinating Center based at the University of California, San Francisco (UCSF) School of Nursing. Site Principal Investigators implement a standardized protocol to recruit PWH to complete the study online or in-person. Questions address demographics; HIV continuum of care indicators; mental and social health; COVID-19 and vaccination knowledge, attitudes, behaviors, and fears; and overall outcomes. Results of this study will contribute to knowledge that can inform responses to future public health crises to minimize their impacts on vulnerable populations such as PWH., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Association of Nurses in AIDS Care.)

Human cancers induce a chaotic, dysfunctional vasculature that promotes tumor growth and blunts most current therapies; however, the mechanisms underlying the induction of a dysfunctional vasculature have been unclear. Here, we show that split end (SPEN), a transcription repressor, coordinates rRNA synthesis in endothelial cells (ECs) and is required for physiological and tumor angiogenesis. SPEN deficiency attenuated EC proliferation and blunted retinal angiogenesis, which was attributed to p53 activation. Furthermore, SPEN knockdown activated p53 by upregulating noncoding promoter RNA (pRNA), which represses rRNA transcription and triggers p53-mediated nucleolar stress. In human cancer biopsies, a low endothelial SPEN level correlated with extended overall survival. In mice, endothelial SPEN deficiency compromised rRNA expression and repressed tumor growth and metastasis by normalizing tumor vessels, and this was abrogated by p53 haploinsufficiency. rRNA gene transcription is driven by RNA polymerase I (RNPI). We found that CX-5461, an RNPI inhibitor, recapitulated the effect of Spen ablation on tumor vessel normalization and combining CX-5461 with cisplatin substantially improved the efficacy of treating tumors in mice. Together, these results demonstrate that SPEN is required for angiogenesis by repressing pRNA to enable rRNA gene transcription and ribosomal biogenesis and that RNPI represents a target for tumor vessel normalization therapy of cancer.

Checkpoint inhibitors such as PD-1/PD-L1 antibody therapeutics are a promising option for the treatment of multiple cancers. Due to the inherent limitations of antibodies, great efforts have been devoted to developing small-molecule PD-1/PD-L1 signaling pathway inhibitors. In this study we established a high-throughput AlphaLISA assay to discover small molecules with new skeletons that could block PD-1/PD-L1 interaction. We screened a small-molecule library of 4169 compounds including natural products, FDA approved drugs and other synthetic compounds. Among the 8 potential hits, we found that cisplatin, a first-line chemotherapeutic drug, reduced AlphaLISA signal with an EC 50 of 8.3 ± 2.2 μM. Furthermore, we showed that cisplatin-DMSO adduct, but not semplice cisplatin, inhibited PD-1/PD-L1 interaction. Thus, we assessed several commercial platinum (II) compounds, and found that bis(benzonitrile) dichloroplatinum (II) disturbed PD-1/PD-L1 interaction (EC 50  = 13.2 ± 3.5 μM). Its inhibitory activity on PD-1/PD-L1 interaction was confirmed in co-immunoprecipitation and PD-1/PD-L1 signaling pathway blockade bioassays. Surface plasmon resonance assay revealed that bis(benzonitrile) dichloroplatinum (II) bound to PD-1 (K D  = 2.08 μM) but not PD-L1. In immune-competent wild-type mice but not in immunodeficient nude mice, bis(benzonitrile) dichloroplatinum (II) (7.5 mg/kg, i.p., every 3 days) significantly suppressed the growth of MC38 colorectal cancer xenografts with increasing tumor-infiltrating T cells. These data highlight that platinum compounds are potential immune checkpoint inhibitors for the treatment of cancers., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Photonic integrated circuits have the potential to pervade into multiple applications traditionally limited to bulk optics. Of particular interest for new applications are ferroelectrics such as Lithium Niobate, which exhibit a large Pockels effect, but are difficult to process via dry etching. Here we demonstrate that diamond-like carbon (DLC) is a superior material for the manufacturing of photonic integrated circuits based on ferroelectrics, specifically LiNbO 3 . Using DLC as a hard mask, we demonstrate the fabrication of deeply etched, tightly confining, low loss waveguides with losses as low as 4 dB/m. In contrast to widely employed ridge waveguides, this approach benefits from a more than one order of magnitude higher area integration density while maintaining efficient electro-optical modulation, low loss, and offering a route for efficient optical fiber interfaces. As a proof of concept, we demonstrate a III-V/LiNbO 3 based laser with sub-kHz intrinsic linewidth and tuning rate of 0.7 PHz/s with excellent linearity and CMOS-compatible driving voltage. We also demonstrated a MZM modulator with a 1.73 cm length and a halfwave voltage of 1.94 V., (© 2023. Springer Nature Limited.)

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m 6 A and mRNA, identified a variety of uncharacterized m 6 A binding proteins, and validated SRSF7 as a potential m 6 A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions., (© 2023. Science China Press.)

The availability of thin-film lithium niobate on insulator (LNOI) and advances in processing have led to the emergence of fully integrated LiNbO 3 electro-optic devices. Yet to date, LiNbO 3 photonic integrated circuits have mostly been fabricated using non-standard etching techniques and partially etched waveguides, that lack the reproducibility achieved in silicon photonics. Widespread application of thin-film LiNbO 3 requires a reliable solution with precise lithographic control. Here we demonstrate a heterogeneously integrated LiNbO 3 photonic platform employing wafer-scale bonding of thin-film LiNbO 3 to silicon nitride (Si 3 N 4 ) photonic integrated circuits. The platform maintains the low propagation loss (<0.1 dB/cm) and efficient fiber-to-chip coupling (<2.5 dB per facet) of the Si 3 N 4 waveguides and provides a link between passive Si 3 N 4 circuits and electro-optic components with adiabatic mode converters experiencing insertion losses below 0.1 dB. Using this approach we demonstrate several key applications, thus providing a scalable, foundry-ready solution to complex LiNbO 3 integrated photonic circuits., (© 2023. The Author(s).)

Background: The digital economy based on the internet and IT is developing rapidly in China, which makes a profound impact on urban environmental quality and residents' health activities. Thus, this study introduces environmental pollution as a mediating variable based on Grossman's health production function to explore the impact of digital economic development on the health of the population and its influence path., Methods: Based on the panel data of 279 prefecture-level cities in China from 2011 to 2017, this paper investigates the acting mechanism of digital economic development on residents' health by employing a combination of mediating effects model and spatial Durbin model., Results: The development of digital economy makes direct improvement on residents' health condition, which is also obtained indirectly by means of environmental pollution mitigation. Besides, from the perspective of spatial spillover effect, the development of digital economy also has a significant promoting effect on the health of adjacent urban residents, and further analysis reveals that the promoting effect in the central and western regions of China is more pronounced than that in the eastern region., Conclusions: Digital economy can have a direct promoting effect on the health of residents, and environmental pollution has an intermediary effect between digital economy and residents' health; At the same time, there is also a regional heterogeneity among the three relationships. Therefore, this paper believes that the government should continue to formulate and implement scientific digital economy development policies at the macro and micro levels to narrow the regional digital divide, improve environmental quality and enhance the health level of residents., (© 2023. The Author(s).)

Fused furans are commonly found units in natural products and medicinal molecules, and methods for their introduction are of fundamental importance. Here we report one-pot cycloadditions of ethynyl indoloxazolidones with 1,3-cyclohexanediones enabled by copper catalysis, leading to a series of functionalized furan derivatives in good yields. This method features mild reaction conditions, high efficiency, and wide substrate scope.

Lobelia species, as rich source of the alkaloid lobeline which has been shown to have important biological activity, have been used in folk medicine throughout East Asia to treat various diseases. However, Lobelia is a complex and varied genus in East Asia and is thus difficult to identify. Genomic resources would aid identification, however the availability of such information is poor, preventing a clear understanding of their evolutionary history from being established. To close this gap in the available genomic data, in this study, 17 plastomes of East Asian lobelias were newly sequenced and assembled. Although the plastomes of Lobelia sect. Hypsela , L. sect. Speirema , and L. sect. Rhynchopetalum shared the gene structure, the inverted repeat (IR)/large single copy (LSC) boundaries, genome size, and the number of repeats were variable, indicating the non-conservative nature of plastome evolution within these sections. However, the genomes of the Lobelia sect. Delostemon and L. sect. Stenotium showed rearrangements, revealing that these two sections might have undergone different evolutionary histories. We assessed nine hotspot genes and 27-51 simple sequence repeat motifs, which will also serve as valuable DNA barcode regions in future population genetics studies and for the delineation of plant species. Our phylogenetic analysis resolved the evolutionary positions of the five sections in agreement with previous evolutionary trees based on morphological features. Although phylogenetic reconstruction of Lobelioideae based on the rpoC2 gene has rarely been performed, our results indicated that it contains a considerable amount of phylogenetic information and offers great promise for further phylogenetic analysis of Lobelioideae. Our site-specific model identified 173 sites under highly positive selections. The branch-site model exhibited 11 positive selection sites involving four genes in the East Asian branches. These four genes may play critical roles in the adaptation of East Asian taxa to diverse environments. Our study is the first to detect plastome organization, phylogenetic utility, and signatures of positive selection in the plastomes of East Asian lobelias, which will help to further advance taxonomic and evolutionary studies and the utilization of medicinal plant resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Xie, Liu, Wang and Li.)

Pteris laeta Wall., as a traditional tea, is popular in Southwest China, but its role in preventing cognitive impairment is unclear. In this study, Pteris laeta Wall. extracts (PW) and its active compounds were evaluated for preventive effects on Alzheimer's disease (AD) in vivo and in vitro . The results showed that PW diminished oxidative stress damage and apoptosis of Aβ-induced HT22 cells and also rescued cognitive deficits, and ameliorated pathological injury and inflammatory response in APP/PS1 mice. Besides, a new pterosin sesquiterpene, named pterosinsade A (PA), and nine known compounds were discovered from the EtOAc extract that possessed the best neuroprotective activity. PA reduced apoptosis of APP-overexpressing neural stem cells and promoted their proliferation and neuronal differentiation. Meanwhile, PW and PA promoted hippocampal neurogenesis, which proved to be associated with activating the Wnt signaling pathway. These findings suggest that PW and PA are candidates for AD prevention.

In regard to membrane-based technologies of wastewater reclamation, the reported key foulants were faced with dilemma that they could not be effectively separated and extracted from reclaimed water for thorough investigation. In this study, the crucial foulants were proposed as "critical minority fraction (F CM )", representing the fraction with molecular weight (MW) > 100 kDa which could be easily separated by physical filtration using MW cut-off membrane of 100 kDa with fairly high recovery ratio. F CM with low dissolved organic carbon (DOC) concentration (∼1 mg/L) accounted for less than 20% of the total DOC in reclaimed water, while contributed to more than 90% of the membrane fouling, and thus F CM could be considered as a "perfect criminal" causing membrane fouling. Furthermore, pivotal fouling mechanism was attributed to the significant attractive force between F CM and membranes, which led to severe fouling development due to the aggregation of F CM on membrane surface. Fluorescent chromophores of F CM were concentrated in regions of proteins and soluble microbial products, with proteins and polysaccharides accounted for 45.2% and 25.1% of the total DOC, specifically. F CM was further fractionated into six fractions, among which hydrophobic acids and hydrophobic neutrals were the dominant components in terms of DOC content (∼80%) as well as fouling contribution. Regarding to these pronounced properties of F CM , targeted fouling control strategies including ozonation and coagulation were applied and proved to achieve remarkable fouling control effect. High-performance size-exclusion chromatography results suggested that ozonation achieved distinct transformation of F CM into low MW fractions, while coagulation removed F CM directly, thus leading to effective fouling alleviation. Therefore, the investigation of the critical foulants was expected to help glean valuable insight into the fouling mechanism and develop targeted fouling control technologies in practical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Early works 1 and recent advances in thin-film lithium niobate (LiNbO 3 ) on insulator have enabled low-loss photonic integrated circuits 2,3 , modulators with improved half-wave voltage 4,5 , electro-optic frequency combs 6 and on-chip electro-optic devices, with applications ranging from microwave photonics to microwave-to-optical quantum interfaces 7 . Although recent advances have demonstrated tunable integrated lasers based on LiNbO 3 (refs. 8,9 ), the full potential of this platform to demonstrate frequency-agile, narrow-linewidth integrated lasers has not been achieved. Here we report such a laser with a fast tuning rate based on a hybrid silicon nitride (Si 3 N 4 )-LiNbO 3 photonic platform and demonstrate its use for coherent laser ranging. Our platform is based on heterogeneous integration of ultralow-loss Si 3 N 4 photonic integrated circuits with thin-film LiNbO 3 through direct bonding at the wafer level, in contrast to previously demonstrated chiplet-level integration 10 , featuring low propagation loss of 8.5 decibels per metre, enabling narrow-linewidth lasing (intrinsic linewidth of 3 kilohertz) by self-injection locking to a laser diode. The hybrid mode of the resonator allows electro-optic laser frequency tuning at a speed of 12 × 10 15  hertz per second with high linearity and low hysteresis while retaining the narrow linewidth. Using a hybrid integrated laser, we perform a proof-of-concept coherent optical ranging (FMCW LiDAR) experiment. Endowing Si 3 N 4 photonic integrated circuits with LiNbO 3 creates a platform that combines the individual advantages of thin-film LiNbO 3 with those of Si 3 N 4 , which show precise lithographic control, mature manufacturing and ultralow loss 11,12 ., (© 2023. The Author(s).)

Objective: Mycobacterium tuberculosis /human immunodeficiency virus (MTB/HIV) coinfection has become an urgent problem in the field of prevention and control of infectious diseases in recent years. Adoptive cellular immunotherapy using antigen-specific T-cell receptor (TCR) engineered T cells which recognize the specific antigen artificially may have tremendous potential in anti-MTB/HIV coinfection. We have previously successfully identified a MTB Ag85B 199-207 and HIV-1 Env 120-128 peptide-bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A∗0201 + healthy individual and have further studied that how residues on the predicted complementarity determining region (CDR) 3 of the β chain contribute to the bispecific TCR contact with the peptide-MHC. However, it is not clear which amino acids in the predicted CDR3α of the bispecific TCR play a crucial role in ligand recognition., Methods: The variants in the CDR3α of the bispecific TCR were generated using alanine substitution. We then evaluated the immune effects of the five variants on T-cell recognition upon encounter with the MTB or HIV-1 antigen., Results: Mutation of two amino acids (E112A, Y115A) in CDR3α of the bispecific TCR caused a markedly diminished T-cell response to antigen, whereas mutation of the other three amino acids (S113A, P114A, S116A) resulted in completely eliminated response., Conclusion: This study demonstrates that Ser 113 , Pro 114 and Ser 116 in CDR3α of the bispecific TCR are especially important for antigen recognition. These results will pave the way for the future development of an improved high-affinity bispecific TCR for use in adoptive cellular immunotherapy for MTB/HIV coinfected patients., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9}  GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

The ability to amplify optical signals is of pivotal importance across science and technology typically using rare-earth-doped fibres or gain media based on III-V semiconductors. A different physical process to amplify optical signals is to use the Kerr nonlinearity of optical fibres through parametric interactions 1,2 . Pioneering work demonstrated continuous-wave net-gain travelling-wave parametric amplification in fibres 3 , enabling, for example, phase-sensitive (that is, noiseless) amplification 4 , link span increase 5 , signal regeneration and nonlinear phase noise mitigation 6 . Despite great progress 7-15 , all photonic integrated circuit-based demonstrations of net parametric gain have necessitated pulsed lasers, limiting their practical use. Until now, only bulk micromachined periodically poled lithium niobate (PPLN) waveguide chips have achieved continuous-wave gain 16,17 , yet their integration with silicon-wafer-based photonic circuits has not been shown. Here we demonstrate a photonic-integrated-circuit-based travelling-wave optical parametric amplifier with net signal gain in the continuous-wave regime. Using ultralow-loss, dispersion-engineered, metre-long, Si 3 N 4 photonic integrated circuits 18 on a silicon chip of dimensions 5 × 5 mm 2 , we achieve a continuous parametric gain of 12 dB that exceeds both the on-chip optical propagation loss and fibre-chip-fibre coupling losses in the telecommunication C band. Our work demonstrates the potential of photonic-integrated-circuit-based parametric amplifiers that have lithographically controlled gain spectrum, compact footprint, resilience to optical feedback and quantum-limited performance, and can operate in the wavelength ranges from visible to mid-infrared and outside conventional rare-earth amplification bands., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study sought to investigate the impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease. Methods: We retrospectively analyzed clinical data of male patients diagnosed with suspected coronary microvascular dysfunction (CMD) in the First Hospital of Shanxi Medical University between December 2015 and August 2021. All patients underwent the one-day rest and stress 13 N-ammonia positron emission tomography myocardial perfusion imaging. Overall obesity was defined by body mass index (BMI) ≥28 kg/m 2 and abdominal obesity was defined by waist circumference ≥90 cm. Hyperemic myocardial blood flow (MBF)<2.3 ml·min -1 ·g -1 or coronary flow reserve (CFR)<2.5 were referred as CMD. All patients were grouped based on their BMI and waist circumference. MBF, CFR, the incidence of CMD, hemodynamic parameters, and cardiac function were compared among the groups. Results: A total of 136 patients were included . According to BMI and waist circumference, patients were categorized into 3 groups: control group ( n =45), simple abdominal obesity group ( n =53) and compound obesity group ( n =38). Resting MBF did not differ between groups ( F =0.02, P =0.994). Compared with the control group, hyperemic MBF was significantly lower in the simple abdominal obesity and compound obesity groups ((2.82±0.64) ml·min -1 ·g -1 , (2.44±0.85) ml·min -1 ·g -1 and (2.49±0.71) ml·min -1 ·g -1 , both P <0.05, respectively). Hyperemic MBF was comparable among the groups of patients with obesity ( P =0.772). CFR was significantly lower in the simle abdominal obesity group compared with the control group (2.87±0.99 vs . 3.32±0.62, P =0.012). Compared with the control group, CFR tended to be lower in the compound obesity group (3.02±0.91 vs . 3.32±0.62, P =0.117). The incidence of CMD was significantly higher in both the simple abdominal obesity and compound obesity groups than in the control group (62.3%, 52.6% vs . 22.2%, both P <0.01, respectively). Waist circumference was an independent risk factor for male CMD ( OR =1.057, 95% CI: 1.013-1.103, P =0.011). Conclusions: In male patients with non-obstructive coronary artery disease, abdominal obesity is associated with decreased coronary microvascular function. Male patients with simple abdominal obesity face the highest risk of CMD.

Metal halide perovskite ferroelectrics possess various physical characteristics such as piezoelectric and pyroelectric effects, which could broaden the application of perovskite ferroelectrics and enhance the optoelectronic performance. Therefore, it is promising to combine multiple effects to optimize the performance of the self-powered PDs. Herein, patterned 2D ferroelectric perovskite (PMA) 2 PbCl 4 microbelt arrays were demonstrated through a PDMS template-assisted antisolvent crystallization method. The perovskite arrays based flexible photodetectors exhibited fine self-powered photodetection performance under 320 nm illumination and much enhanced reproducibility compared with the randomly distributed single-crystal microbelts-based PDs. Furthermore, by introducing the piezo-phototronic effect, the performance of the flexible PD was greatly enhanced. Under an external tensile strain of 0.71%, the responsivity was enhanced by 185% from 84 to 155.5 mA/W. Our findings offer the advancement of comprehensively utilizing various physical characteristics of the ferroelectrics for novel ferroelectric optoelectronics.

Quantum information, communication, and sensing rely on the generation and control of quantum correlations in complementary degrees of freedom. Free electrons coupled to photonics promise novel hybrid quantum technologies, although single-particle correlations and entanglement have yet to be shown. In this work, we demonstrate the preparation of electron-photon pair states using the phase-matched interaction of free electrons with the evanescent vacuum field of a photonic chip-based optical microresonator. Spontaneous inelastic scattering produces intracavity photons coincident with energy-shifted electrons, which we employ for noise-suppressed optical mode imaging. This parametric pair-state preparation will underpin the future development of free-electron quantum optics, providing a route to quantum-enhanced imaging, electron-photon entanglement, and heralded single-electron and Fock-state photon sources.