[A longitudinal study of subjective olfactory function post-operatively in chronic rhinosinusitis patients with asthma and analysis of influencing factors].

Objective:To evaluate the subjective olfactory function in chronic sinusitis（CRS）patients with asthma after nasal endoscopic surgery and associated factors that may affect olfactory function. Methods：The study included 90 CRS patients with asthma from January 2008 to December 2020，and all of them underwent endoscopic sinus surgery（ESS）. VAS score of olfactory function before and after surgery were collected，and the data at baseline，3 months，6 months，1 year，3 years，5 years，8 years and 10 years after surgery were compared. Factors affecting olfactory function were analyzed in a generalized mixed linear model，which including age，surgical procedure，allergic rhinitis and so on.Results： The olfactory VAS scores were significantly lower at 3 months，6 months，1 year，3 years，and 5 years postoperatively compared with baseline，and the difference was statistically significant（P<0.05）.Olfactory VAS scores at 8 and 10 years postoperatively were not statistically different from baseline（P>0.05）.Age（≥60 years），aspirin intolerance syndrome，Lund-Kennedy score，modified sinus CT olfactory cleft score，and follow-up time were risk factors, and radical sinus surgery is a protective factor.Conclusion：Subjective olfactory scores in CRS patients with asthma after ESS remain relatively stable for 5 years postoperatively.Prior history of surgery did not affect postoperative subjective olfactory scores. Age，aspirin intolerance syndrome, Lund-Kennedy score，modified sinus CT olfactory cleft score, follow-up time，and surgical approach were strongly associated with subjective olfactory scores in CRS patients with asthma，and radical surgery had a protective effect on olfaction.

Moving beyond hotspots of HIV prevalence to geospatial hotspots of UNAIDS 95-95-95 targets in sub-Saharan Africa.

The HIV epidemic in sub-Saharan Africa displays a varied geographical distribution, with particular regions termed as HIV hotspots due to a higher prevalence of infection. Addressing these hotspots is essential for controlling the epidemic. However, these regions, influenced by historical factors, challenge standard interventions. Legacy effects-the lasting impact of past events-play a substantial role in the persistence of these hotspots. To address this challenge of the standard interventions, we propose a shift towards the UNAIDS 95-95-95 targets. Spatial analysis of HIV viral load and antiretroviral therapy coverage can provide a more comprehensive perspective on the epidemic's dynamics. Studies in Zambia and Zimbabwe, using this approach, have revealed disparities in HIV care metrics across regions. By focusing on the UNAIDS 95-95-95 targets, more effective control strategies can be designed, with consideration of both historical and current factors. This approach would offer a solution-oriented strategy, emphasising tailored interventions based on specific regional needs.

Modulation of the strength of weak S-H⋯O hydrogen-bond: Spectroscopic study of the complexes of 2-flurothiophenol with methanol and ethanol.

Spectroscopic exploration of sulfur-centered hydrogen bonding involving a thiol group (S-H) as the hydrogen bond donor is scarce in the literature. Herein, we have investigated 1:1 complexes of 2-fluorothiophenol (2-FTP) with methanol (MeOH) and ethanol (EtOH) in the gas phase to examine the physical characteristics and strength of the S-H⋯O hydrogen bond. Structures, conformations, and the strength of the S-H⋯O interaction are investigated by measuring the electronic and Infrared (IR) spectra of the two complexes employing resonant two-photon ionization, UV-UV hole-burning, and IR-UV double resonance spectroscopic techniques combined with quantum chemical calculations. Three conformers of 2-FTP⋯MeOH and two conformers of 2-FTP⋯EtOH have been detected in the experiment. A comparison of the IR spectra obtained from the experiment with those of the low-energy conformers of 2-FTP⋯MeOH and 2-FTP⋯EtOH predicted from the theory confirms that all the observed conformers of the two complexes are primarily S-H⋯O hydrogen bonded. The IR red-shifts found in the S-H stretching frequencies in 2-FTP⋯MeOH and 2-FTP⋯EtOH concerning that in 2-FTP are ∼76 and ∼88 cm-1, respectively, which are much larger than that was reported earlier in the 2-FTP⋯H2O complex (30 cm-1). The strength and physical nature of different noncovalent interactions, including the S-H⋯O hydrogen bond existing in the complexes, are further analyzed using natural bond orbital analysis, quantum theory of atoms in molecules, and localized molecular orbital-energy decomposition analysis. The current investigation reveals that the S-H⋯O hydrogen bond can be strengthened by judicial choices of the hydrogen bond acceptors of higher proton affinities.

Adherence to 24-Hour Movement Guidelines Among Chinese Older Adults: Prevalence, Correlates, and Associations With Physical and Mental Health Outcomes.

BACKGROUND: It is known that 24-hour movement behaviors, including physical activity (PA), sedentary behavior (SB), and sleep, are crucial components affecting older adults' health. Canadian 24-hour movement guidelines for older adults were launched in 2020, emphasizing the combined role of these 3 movement behaviors in promoting older adults' health. However, research on the prevalence and correlates of guideline adherence and its associations with health-related outcomes is limited, especially among Chinese older adults. OBJECTIVE: This study aimed to investigate the prevalence and correlates of meeting 24-hour movement guidelines among Chinese older adults. Furthermore, this study aimed to examine the associations of guideline adherence with older adults' physical and mental health outcomes. METHODS: Using a stratified cluster random sampling approach, a total of 4562 older adults (mean age 67.68 years, SD 5.03 years; female proportion: 2544/4562, 55.8%) were recruited from the latest provincial health surveillance of Hubei China from July 25 to November 19, 2020. Measures included demographics, movement behaviors (PA, SB, and sleep), BMI, waist circumference, waist-hip ratio (WHR), percentage body fat (PBF), systolic and diastolic blood pressure, physical fitness, depressive symptoms, and loneliness. Generalized linear mixed models were employed to examine the associations between variables using SPSS 28.0 (IBM Corp). RESULTS: Only 1.8% (83/4562) of participants met all 3 movement guidelines, while 32.1% (1466/4562), 3.4% (155/4562), and 66.4% (3031/4562) met the individual behavioral guidelines for PA, SB, and sleep, respectively. Participants who were older, were female, and lived in municipalities with lower economic levels were less likely to meet all 3 movement guidelines. Adhering to individual or combined movement guidelines was associated with greater physical fitness and lower values of BMI, waist circumference, WHR, PBF, depressive symptoms, and loneliness, with the exception of the relationship of SB+sleep guidelines with loneliness. Furthermore, only meeting SB guidelines or meeting both PA and SB guidelines was associated with lower systolic blood pressure. CONCLUSIONS: This is the first study to investigate adherence to 24-hour movement guidelines among Chinese older adults with regard to prevalence, correlates, and associations with physical and mental health outcomes. The findings emphasize the urgent need for promoting healthy movement behaviors among Chinese older adults. Future interventions to improve older adults' physical and mental health should involve enhancing their overall movement behaviors and should consider demographic differences.

Efficacy and advantage of immunotherapy for melanoma via intramuscular co-expression of plasmid-encoded PD-1 and CTLA-4 scFvs.

Immunotherapy, in the shape of immune checkpoint inhibitors (ICIs), has completely changed the treatment of cancer. However, the increasing expense of treatment and the frequency of immune-related side effects, which are frequently associated with combination antibody therapies and Fc fragment of antibody, have limited the patient's ability to benefit from these treatments. Herein, we presented the therapeutic effects of the plasmid-encoded PD-1 and CTLA-4 scFvs (single-chain variable fragment) for melanoma via an optimized intramuscular gene delivery system. After a single injection, the plasmid-encoded ICI scFv in mouse sera continued to be above 150 ng/mL for 3 weeks and reached peak amounts of 600 ng/mL. Intramuscular delivery of plasmid encoding PD-1 and CTLA-4 scFvs significantly changed the tumor microenvironment, delayed tumor growth, and prolonged survival in melanoma-bearing mice. Furthermore, no significant toxicity was observed, suggesting that this approach could improve the biosafety of ICIs combination therapy. Overall, the expression of ICI scFvs in vivo using intramuscular plasmid delivery could potentially develop into a reliable, affordable, and safe immunotherapy technique, expanding the range of antibody-based gene therapy systems that are available.

Unexpected Stress Overshoot in Extensional Flow of Star Polymer Melts.

Previous studies have shown that the nonlinear rheological behavior of 3-arm star polymer melts in fast extensional flow is identical to that of linear polymers with the same span molecular weight, because the star polymers are highly aligned and have a similar conformation as the corresponding linear polymers. However, with more arms, it would be more difficult for the stars to be aligned like linear chains, and the nonlinear extensional rheology of star polymers with more arms under large deformations has not been investigated yet. Here we show that the star polystyrene (8-10 arms) melts behave differently from the linear polystyrenes. A transient stress overshoot is observed in the fast extensional flow, probably due to the difference in entanglement density near and far away from the branch point.

Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action.

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain and, more importantly, preventing its transition to a chronic state. In a mouse model of post-surgical pain, local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. Importantly, preemptive drug treatment also inhibited the transition of post-surgical pain to a prolonged state. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways, and indirect pain relief by attenuating immune cell recruitment. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.

Social support, psychological capital, multidimensional job burnout, and turnover intention of primary medical staff: a path analysis drawing on conservation of resources theory.

BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.

Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4.

The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.

Characterizing the Perceived Need for CRC Screening among the Elderly Living in Rural Areas in the Pacific Northwest US: Roles of Miscommunication, Experience of Discrimination, and Dependence.

PURPOSE: Increasing the perceived need for CRC screening can facilitate undertaking CRC screening. This study aims to identify factors associated with the need for CRC screening in rural populations. DESIGN: A cross-sectional online survey. SETTING: The survey was conducted in June - September 2022 in the rural areas of Alaska, Idaho, Oregon, and Washington, US. SUBJECTS: The subjects of this study were 250 adults (completion rate: 65%) aged 45-75 residing in rural Alaska, Idaho, Oregon, and Washington. MEASURES: Perceived need for CRC screening, internet usage for health purposes, demographics, and intrapersonal, interpersonal, community, and environmental characteristics. RESULTS: Perceived need for CRC screening were negatively associated with patient-provider miscommunication (ß = -.23, P < .001) and perceived discrimination (ß = -.21, P < .001), cancer fatalism (ß = -.16, P < .05), individualism (ß = -.15, P < .05), and dependence on community (ß = -.11, P < .05), but positively with compliance with social norms (ß = .16, P < .05), trust in health care providers (ß = .16, P < .05), knowledge about colorectal cancer (ß = .12, P < .05). CONCLUSIONS: Our study showed potential individual and situational characteristics that might help increase colorectal cancer screening. Future efforts might consider addressing discrimination in health care settings, improving patient-provider communication, and tailoring messaging to reflect the rural culture.

The impact of digital inclusive financial development on local government expenditure: Evidence from China.

This paper investigates the impact of digital inclusive financial development on local government expenditure incentives at the income level. It does so by constructing a multi-level government Dynamic Stochastic General Equilibrium (DSGE) model that incorporates the financial sector. By employing empirical methods that involve uncertainty shocks and counterfactual simulations, the research yields several key findings. Firstly, the development of digital inclusive finance contributes to breaking down the urban-rural dual financial structure, thus facilitating balanced economic development within regions. Secondly, it reduces the proportion of financially excluded areas, accelerates fiscal decentralization, leading to an increase in local government fiscal revenue, and, consequently, an expansion of local fiscal expenditures. Thirdly, at a certain stage of digital inclusive finance development, it tends to crowd out residents' investment and consumption. Therefore, the decentralization of fiscal power and the expansion of local government expenditure at this stage may paradoxically inhibit regional economic growth. The study's conclusions validate the significant impact of digital inclusive finance on local government incentives at the income level.

Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron.

Ferroptosis of intestinal epithelial cells (IECs) had been identified as a key factor in the development of ulcerative colitis (UC). Therefore, targeted inhibition of ferroptosis may provide a new strategy for the treatment of UC. Isorhamnetin (ISO) was an O-methylated flavonol with therapeutic effects on a variety of diseases, such as cardiovascular disease, neurological disorders and tumors. However, the role and mechanism of ISO in ferroptosis and associated colitis were rarely investigated. In this study, we demonstrated that ISO could effectively alleviate intestinal inflammation by inhibiting ferroptosis of IECs in DSS-induced mice. Moreover, our results shown that ISO acted as a potent and common ferroptosis inhibitor in multiple human and murine cell lines. Mechanistically, ISO inhibited ferroptosis independent of its previously reported targets MEK1 and PI3K, but alleviated oxidative stress by targeting and activating NRF2. Furthermore, ISO could also directly chelate iron to hinder ferroptosis. In conclusion, our study indicated that ISO as a novel potential ferroptosis inhibitor, providing a promising therapeutic strategy for ferroptosis-related colitis.

Anti-rheumatoid arthritis effects of traditional Chinese medicine Fufang Xiaohuoluo pill on collagen-induced arthritis rats and MH7A cells.

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1ß (IL1ß), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1ß and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/ß (IKKα/ß), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL.

Neurofibromatosis type 1 with huge intrathoracic meningoceles misdiagnosed as pleural effusion: A case report and literature review.

BACKGROUND: Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'. CASE PRESENTATION: In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients. CONCLUSIONS: In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.

Associations between genetic mutations in different SARS-CoV-2 strains and negative conversion time of viral RNA among imported cases in Hangzhou: A cross-sectional study.

PURPOSE: Previous studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on factors that influence the achievement of negative conversion of viral RNA. This study aimed to investigate the effects of the genetic mutations in different SARS-CoV-2 strains on the negative conversion time (NCT) among imported cases in Hangzhou, Zhejiang Province, China, in order to provide valuable insights for developing targeted epidemic prevention guidelines. METHODS: This retrospective study involved 146 imported SARS-CoV-2 cases in Hangzhou from 8 April 2021 to 11 June 2022. We compared the SARS-CoV-2-specific indicators, clinical indexes, and NCT among the wild-type (WT), Delta, and Omicron groups. Spearman correlation analysis was used to identify the correlations of NCT with mutation types/frequencies. RESULTS: The mean age of the imported cases was 35.3 (SD: 12.3) years, with 71.92 % males and 28.08 % females. The mean cycle threshold (Ct) values of open reading frame 1ab (ORF1ab) and nucleocapsid (N) RNA were 25.17 (SD: 6.44) and 23.4 (SD: 6.76), respectively. The mutations of SARS-CoV-2 strains were mainly located in N, membrane (M), spike (S), ORF1a, ORF1b, ORF3a, ORF6, and ORF9b genes among the WT, Delta, and Omicron groups. NCT was significantly prolonged in the WT and Delta groups compared to the Omicron group. T lymphocyte, white blood cell, eosinophil, and basophil counts were dramatically higher in the WT group than the Delta group. White blood cell, red blood cell, and basophil counts were significantly lower in the Delta group than the Omicron group. Spearman correlation analysis revealed a significant correlation between the NCT of viral RNA and mutation types of viral genes of WT and Omicron strains. Additionally, NCT was markedly negatively correlated with the frequencies of five mutations in Omicron strains (ORF1b:P1223L, ORF1b:R1315C, ORF1b:T2163I, ORF3a:T223I, and ORF6:D61L). CONCLUSIONS: This study indicates that five mutations in Omicron strains (ORF1b:P1223L/R1315C/T2163I, ORF3a:T223I and ORF6:D61L) shortened NCT in imported SARS-CoV-2 cases.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Causality between sleep traits and the risk of frailty: a Mendelian randomization study.

Background: Research based on observation has demonstrated a relationship between sleep traits and frailty; however, it remains uncertain if this correlation indicates causation. The purpose of this study was to look at the causal relationship that exists between frailty and sleep traits. Method: Using summaries from a genome-wide association study of self-reported sleep features and frailty index, we performed a bidirectional Mendelian randomization (MR) analysis. Examining the causal relationships between seven sleep-related traits and frailty was the goal. The major method used to calculate effect estimates was the inverse-variance weighted method, supplemented by the weighted median and MR-Egger approaches. The study investigated pleiotropy and heterogeneity using several methodologies, such as the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test. We took multivariate Mendelian randomization and genetic correlations between related traits to enhance the confidence of the results. Furthermore, we used MRlap to correct for any estimation bias due to sample overlap. Results: Insomnia, napping during the day, and sleep apnea syndrome exhibited a positive connection with the frailty index in forward MR analysis. Conversely, there is a negative link between getting up in the morning, snoring and sleep duration with the frailty index. During the reverse MR analysis, the frailty index exhibited a positive correlation with insomnia, napping during the day, and sleep apnea syndrome, while demonstrating a negative correlation with sleep duration. There was no direct correlation between snoring, chronotype, and frailty. In MVMR analyses, the causal effect of sleep characteristics on frailty indices remained consistent after adjusting for potential confounders including BMI, smoking, and triglycerides. Conclusion: The findings of our investigation yield novel evidence that substantiates the notion of a bidirectional causal connection between sleep traits and frailty. Through the optimization of sleep, it is potentially feasible to hinder, postpone, or even reverse the state of frailty, and we proposed relevant interventions.

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

An efficient Fusion-Purification Network for Cervical pap-smear image classification.

BACKGROUND AND OBJECTIVES: In cervical cell diagnostics, autonomous screening technology constitutes the foundation of automated diagnostic systems. Currently, numerous deep learning-based classification techniques have been successfully implemented in the analysis of cervical cell images, yielding favorable outcomes. Nevertheless, efficient discrimination of cervical cells continues to be challenging due to large intra-class and small inter-class variations. The key to dealing with this problem is to capture localized informative differences from cervical cell images and to represent discriminative features efficiently. Existing methods neglect the importance of global morphological information, resulting in inadequate feature representation capability. METHODS: To address this limitation, we propose a novel cervical cell classification model that focuses on purified fusion information. Specifically, we first integrate the detailed texture information and morphological structure features, named cervical pathology information fusion. Second, in order to enhance the discrimination of cervical cell features and address the data redundancy and bias inherent after fusion, we design a cervical purification bottleneck module. This model strikes a balance between leveraging purified features and facilitating high-efficiency discrimination. Furthermore, we intend to unveil a more intricate cervical cell dataset: Cervical Cytopathology Image Dataset (CCID). RESULTS: Extensive experiments on two real-world datasets show that our proposed model outperforms state-of-the-art cervical cell classification models. CONCLUSIONS: The results show that our method can well help pathologists to accurately evaluate cervical smears.

An oleanic acid decorated gold nanorod for highly efficient inhibition of hemagglutinin and visible rapid detection of the influenza virus.

Accurate diagnosis and effective antiviral treatments are urgently needed for the prevention and control of flu caused by influenza viruses. In this study, a novel oleanic acid (OA) functionalized gold nanorod OA-AuNP was prepared through a convenient ligand-exchange reaction. As hemagglutinin (HA) on the viral surface binds strongly to the multiple OA molecules on the surface of the nanoparticle, the prepared OA-AuNP was found to exhibit potent antiviral activity against a wide range of influenza A virus strains. Furthermore, the change in color resulting from the specific binding between HA and OA and the resultant aggregation of the OA-AuNP can be visually observed or measured by UV-vis spectra with a detection limit of 2 and 0.18 hemagglutination units (HAU), respectively, which is comparable to the commercially available influenza colloid gold rapid diagnostic kits. These findings demonstrate the potential of the OA-AuNP for the development of novel multivalent antiviral conjugates and the diagnosis of influenza virus.