Adjustable focusing property of circular Airyprime beam through Fourier space modulation.

Airyprime beams are known for their powerful autofocusing property, which are further enhanced by the introduction of a circular structure-circular Airyprime beam (CAPB). We derive an asymptotic expression of the CAPB in Fourier space (FS) and verify its accuracy by the numerical Fourier transform (FT) method. Through FS modulation on it, adjustable control of autofocusing property of the FS-modulated CAPB can be achieved, whose lower and upper limits can reach 8.7% reduction and 2.6 times enhancement compared to the unmodulated one. The experimental results agree well with the numerical analyses. Our findings offer promising possibilities for efficient particle trapping and enhancing free-space optical communication capabilities.

PM2.5 chemical components are associated with in-hospital case fatality among acute myocardial infarction patients in China.

Recent studies have linked the cardiovascular events with the exposure to ambient fine particulate matter (PM2.5); however, the impact of PM2.5 chemical components on acute myocardial infarction (AMI) case fatality remains poorly understood. To address this gap, we included 178,340 hospitalised patients with AMI utilising the inpatient discharge database from Sichuan, Shanxi, Guangxi, and Guangdong, China spanning 2014-2019. We evaluated exposure to PM2.5 and its components (black carbon (BC), organic matter (OM), sulphate (SO42-), nitrate (NO3-), and ammonium (NH4+)) using bilinear interpolation based on the patient's residential address. We used mixed-effects logistic regression models to investigate the associations of PM2.5 and its five components with in-hospital AMI case fatality. Per interquartile range (IQR) increment in short-term exposure (7-day average) to overall PM2.5 (odds ratio (OR): 1.086, 95 % confidence interval (CI): 1.045-1.128), SO42-(1.063, 1.024-1.104), BC (1.055, 1.023-1.089), OM (1.052, 1.019-1.086, and NO3- (1.045, 1.003-1.089) were significantly associated with high risk of in-hospital AMI case fatality. The ORs per IQR increment in long-term exposure (annual average) were 1.323 (95 % CI: 1.255-1.394) for PM2.5, followed by BC (1.271, 1.210-1.335), OM (1.243, 1.188-1.300), SO42- (1.212, 1.157-1.270), NO3- (1.116, 1.075-1.159), and NH4+ (1.068, 1.031-1.106). Our study suggests that PM2.5 chemical components might be important risk factors for in-hospital AMI case fatality, highlighting the importance of targeted reduction of PM2.5 emissions, particularly BC, OM, and SO42-.

Suppression of RCAN1 alleviated lipid accumulation and mitochondrial fission in diabetic cardiomyopathy.

BACKGROUND: Although metabolic disturbance is a characteristic of diabetic cardiomyopathy (DbCM), the detailed pathogenesis of DbCM remains unknown. METHODS: We used a heart transplantation (HTx) cohort to explore the effect of diabetes mellitus on heart failure (HF) progression dependent of myocardium. Microscopic and ultramicroscopic pathology were used to depict the pathological features of human myocardium of DbCM. We performed targeted metabolomics to characterize the metabolic phenotype of human DbCM. Transcriptomics data were analyzed and weighted gene co-expression network analysis was performed to explore the potential upstream regulator for metabolic remodeling of DbCM. In vivo and in vitro experiments were further conducted to demonstrate the therapeutic effects and molecular mechanisms. RESULTS: DbCM promoted the progression of HF and increased death or HF-rehospitalization after HTx. Lipid accumulation and mitochondrial fission were the obvious pathological features of DbCM myocardium. The concentrations of C14:0-CoA and C16:1-CoA were significantly increased in the myocardium, and they were positively correlated with the accelerated HF progression and RCAN1 expression in DbCM patients. Knockdown of RCAN1 improved cardiac dysfunction, lipid accumulation, and mitochondrial fission in db/db mice. In vitro studies showed that RCAN1 knockdown improved mitochondrial dysfunction in DbCM cardiomyocytes via the RCAN1-p-Drp1 Ser616 axis. CONCLUSIONS: Diabetes is associated with faster progression of HF and causes poor prognosis after HTx, accompanied by metabolic remodeling in the myocardium. Accumulation of long chain acyl-CoA in the myocardium is the metabolic hallmark of human DbCM and is associated with more rapid disease progression for DbCM patients. Upregulation of RCAN1 in the myocardium is associated with the metabolic signatures of DbCM and RCAN1 is a potential therapeutic target for DbCM.

The conditional recurrence-free survival after R0 hepatectomy for locally advanced intrahepatic cholangiocarcinoma: A competing risk analysis based on inflammation-nutritional status.

Background: Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method. Methods: We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators. Results: Considering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set. Conclusions: Conditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.

A novel long noncoding RNA ENST00000597482 serves as a potential biomarker for disease activity and diagnosis of systemic lupus erythematosus.

OBJECTIVES: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. METHODS: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. CONCLUSIONS: LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.

Enzyme-mediated green synthesis of glycosaminoglycans and catalytic process intensification.

Glycosaminoglycans (GAGs) are a family of structurally complex heteropolysaccharides that play pivotal roles in biological functions, including the regulation of cell proliferation, enzyme inhibition, and activation of growth factor receptors. Therefore, the synthesis of GAGs is a hot research topic in drug development. The enzymatic synthesis of GAGs has received widespread attention due to their eco-friendly nature, high regioselectivity, and stereoselectivity. The enhancement of the enzymatic synthesis process is the key to its industrial applications. In this review, we overviewed the construction of more efficient in vitro biomimetic synthesis systems of glycosaminoglycans and presented the different strategies to improve enzyme catalysis, including the combination of chemical and enzymatic methods, solid-phase synthesis, and protein engineering to solve the problems of enzyme stability, separation and purification of the product, preparation of structurally defined sugar chains, etc., and discussed the challenges and opportunities in large-scale green synthesis of GAGs.

The Clinical Association Between the Inflammation-Nutritional Condition and Prognosis of Locally Advanced Intrahepatic Cholangiocarcinoma After R0 Resection: Evidence from Competing Risk and Propensity Matching Analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.

Triclosan-loaded aged microplastics exacerbate oxidative stress and neurotoxicity in Xenopus tropicalis tadpoles via increased bioaccumulation.

Microplastics and chlorine-containing triclosan (TCS) are widespread in aquatic environments and may pose health risks to organisms. However, studies on the combined toxicity of aged microplastics and TCS are limited. To investigate the toxic effects and potential mechanisms associated with co-exposure to TCS adsorbed on aged polyethylene microplastics (aPE-MPs) at environmentally relevant concentrations, a 7-day chronic exposure experiment was conducted using Xenopus tropicalis tadpoles. The results showed that the overall particle size of aPE-MPs decreased after 30 days of UV aging, whereas the increase in specific surface area improved the adsorption capacity of aPE-MPs for TCS, resulting in the bioaccumulation of TCS under dual-exposure conditions in the order of aPE-TCS > PE-TCS > TCS. Co-exposure to aPE-MPs and TCS exacerbated oxidative stress and neurotoxicity to a greater extent than a single exposure. Significant upregulation of pro-symptomatic factors (IL-ß and IL-6) and antioxidant enzyme activities (SOD and CAT) indicated that the aPE-TCS combination caused more severe oxidative stress and inflammation. Molecular docking revealed the molecular mechanism of the direct interaction between TCS and SOD, CAT, and AChE proteins, which explains why aPE-MPs promote the bioaccumulation of TCS, causing increased toxicity upon combined exposure. These results emphasize the need to be aware of the combined toxicity caused by the increased ability of aged microplastics to carry contaminants.

Fine particulate matter (PM2.5) induces testosterone disruption by triggering ferroptosis through SIRT1/HIF-1α signaling pathway in male mice.

Fine particulate matter (PM2.5), a significant component of air pollution particulate matter, is inevitable and closely associated with increasing male reproductive disorder. However, the testicular targets of PM2.5 and its toxicity related molecular mechanisms are still not fully understood. In this study, the conditional knockout (cKO) mice and primary Leydig cells were used to explore the testicular targets of PM2.5 and the related underlying mechanisms. First, apparent the structure impairment of seminiferous tubules, Leydig cells vacuolization, decline of serum testosterone and sperm quality reduction were found in male wild-type (WT) and Sirt1 knockout mice after exposure to PM2.5. Enrichment analyses revealed that differentially expressed genes (DEGs) were enriched in steroid hormone biosynthesis, ferroptosis, and HIF-1 signaling pathway in the mice testes after exposure to PM2.5, which were subsequently verified by the molecular biological analyses. Notably, similar enrichment analyses results were also observed in primary Leydig cells after treatment with PM2.5. In addition, Knockdown of Sirt1 significantly increased PM2.5-induced expression and activation of HIF-1α, which was in parallel to the changes of cellular iron levels, oxidative stress indicators and the ferroptosis markers. In conclusion, this highlights that PM2.5 triggers ferroptosis via SIRT1/HIF-1α signaling pathway to inhibit testosterone synthesis in males. These findings provide a novel research support for the study that PM2.5 causes male reproductive injury.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

Heterogeneous effects of hospital competition on inpatient quality: an analysis of five common diseases in China.

BACKGROUND: Many countries has introduced pro-competition policies in the delivery of healthcare to improve medical quality, including China. With the increasing intensity of competition in China's healthcare market, there are rising concerns among policymakers about the impact of hospital competition on quality. This study investigated heterogeneous effects of hospital competition on inpatient quality. METHODS: We analyzed the inpatient discharge dataset and selected chronic obstructive pulmonary disease (COPD), ischemic stroke, pneumonia, hemorrhagic stroke, and acute myocardial infarction (AMI) as representative diseases. A total of 561,429 patients in Sichuan Province in 2017 and 2019 were included. The outcomes of interest were in-hospital mortality and 30-day unplanned readmissions. The Herfindahl-Hirschman Index was calculated using predicted patient flows to measure hospital competition. To address the spatial correlations of hospitals and the structure of the dataset, the multiple membership multiple classification model was employed for analysis. RESULTS: Amid intensifying competition in the hospital market, our study discerned no marked statistical variance in the risk of inpatient quality across most diseases examined. Amplified competition exhibited a positive correlation with heightened in-hospital mortality for both COPD and pneumonia patients. Elevated competition escalated the risk of 30-day unplanned readmissions for COPD patients, while inversely affecting the risk for AMI patients. CONCLUSIONS: There is the heterogeneous impact of hospital competition on quality across various diseases in China. Policymakers who intend to leverage hospital competition as a tool to enhance healthcare quality must be cognizant of the possible influences of it.

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Is low-dose computed tomography for lung cancer screening conveniently accessible in China? A spatial analysis based on cross-sectional survey.

BACKGROUND: Regular Low-Dose Computed Tomography (LDCT) for lung cancer high-risk population has been proved to improve health outcomes and relieve disease burden efficiently for both individual and society. With geographical impedance becoming the major barrier preventing patients from getting timely healthcare service, this study incorporated health seeking behavior in estimating spatial accessibility of relative scarce LDCT resource in China, thus to provide real-world evidence for future government investment and policy making. METHODS: Taking Sichuan Province in southwest China as the study area, a cross-sectional survey was first carried out to collect actual practice and preferences for seeking LDCT services. Using Computed Tomography (CT) registration data reported by owner institutions representing LDCT services capacity, and grided town-level high-risk population as demand, the Nearest Neighbor Method was then utilized to calculate spatial accessibility of LDCT services. RESULTS: A total of 2,529 valid questionnaires were collected, with only 34.72% of the high-risk populations (746 individuals) followed the recommended annual screening. Participants preferred to travel to municipal-level and above institutions within 60 min for LDCT services. Currently, every thousand high-risk populations own 0.0845 CT scanners in Sichuan Province, with 96.95% able to access LDCT within 60 min and over half within 15 min. Urban areas generally showed better accessibility than rural areas, and the more developed eastern regions were better than the western regions with ethnic minority clusters. CONCLUSIONS: Spatial access to LDCT services is generally convenient in Sichuan Province, but disparity exists between different regions and population groups. Improving LDCT capacity in county-level hospitals as well as promoting health education and policy guidance to the public can optimize efficiency of existing CT resources. Implementing mobile CT services and improving rural public transportation may alleviate emerging disparities in accessing early lung cancer detection.

METTL3-m6A-SIRT1 axis affects autophagic flux contributing to PM2.5-induced inhibition of testosterone production in Leydig cells.

Epidemiological studies have found that long-term inhalation of PM2.5 is closely related to spermatogenesis disorders and infertility, but the underlying molecular mechanism is still unidentified. Testosterone, an essential reproductive hormone produced by Leydig cells, whose synthesis is disrupted by multiple environmental pollutants. In the current study, we explored the role of METTL3-m6A-SIRT1 axis-mediated abnormal autophagy in PM2.5-induced inhibition of testosterone production in in vivo and in vitro models. Our in vivo findings shown that long-term inhalation of PM2.5 decreased sperm count, increased sperm deformity rates, and altered testicular interstitial morphology accompanied by reduced testosterone in serum and testes. Further, data from the in vitro model displayed that exposure to PM2.5 caused an increase in m6A modification and METTL3 levels, followed by a decrease in testosterone levels and autophagy dysfunction in Leydig cells. The knockdown of METTL3 promotes autophagy flux and testosterone production in Leydig cells. Mechanistically, PM2.5 increased METTL3-induced m6A modification of SIRT1 mRNA in Leydig cells, bringing about abnormal autophagy. Subsequently, administration of SRT1720 (a SIRT1 activator) enhanced autophagy and further promoted testosterone biosynthesis. Collectively, our discoveries indicate that METTL3-m6A-SIRT1 axis-mediated autophagic flux contributes to PM2.5-induced inhibition of testosterone biosynthesis. This research offers a novel viewpoint on the mechanism of male reproductive injury following PM2.5 exposure.

Differences in physicochemical, rheological, and prebiotic properties of inulin isolated from five botanical sources and their potential applications.

This study compares the physicochemical and prebiotic properties of inulin isolated from five botanical sources. The average degree of polymerization (DP) for inulin ranged from 5.00 to 13.33. Notably, inulin from Dahlia tubers (DP = 13) and Platycodonis Radix (DP = 8) demonstrated granular, clustered morphology under SEM, semi-crystalline structures via X-ray diffraction, and exhibited shear-thinning behaviors from shear rate 1 s-1 to 500 s-1. In contrast, inulin from Jerusalem artichoke (DP = 5), chicory root (DP = 7), and Asparagi Radix (DP = 5) showcased rough flake morphologies under SEM, amorphous structures in X-ray patterns, and similar shear-thinning behaviors. All inulin types showed acid stability at pH levels below 2.0, with a reducing sugar conversion ratio (RRS) under 1 %. Furthermore, the isolated inulin from the different sources presented prebiotic capacity when added as a sole carbon source in the culture media of the probiotics Lactobacillus paracasei and Bifidobacterium longum. This study provides the properties of inulin from various sources, thereby offering a reference for the selection of appropriate inulin in industrial applications based on the desired characteristics of the final product.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties.

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross- Sectional Studies.

BACKGROUND: Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. OBJECTIVE: We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. METHODS: We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. RESULTS: Compared to non-OI participants, individuals with OI had lower MMSE z-score [ßHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; ßELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment (Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11). The associations were stronger for non-allergy-related OI (ßHRS = -0.36; ßELSA = -0.34) than for allergy-related OI (ßHRS = -0.26; ßELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. CONCLUSION: OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

(3+1)-dimensional Pearcey-Gaussian wave packet with arbitrary velocity driven by flying focus.

The group velocity (GV) modulation of space-time wave packets (STWPs) along the transverse and longitudinal directions in free space is constrained by various factors. To surmount this limitation, a technique called "flying focus" has been developed, which enables the generation of laser pulses with dynamic focal points that can propagate at arbitrary velocities independent of GV. In this Letter, we propose a (3+1)-dimensional Pearcey-Gauss wave packet based on the "flying focus" technique, which exhibits superluminal propagation, transverse focus oscillation, and longitudinal periodic autofocusing. By selecting appropriate parameters, we can flexibly manipulate the position, the size, and the number of focal points- or make the wave packet follow a desired trajectory. This work may pave the way for the advancement of space-time structured light fields.

In vitro assessment of the bacterial stress response and resistance evolution during multidrug-resistant bacterial invasion of the Xenopus tropicalis intestinal tract under typical stresses.

The intestinal microbiome might be both a sink and source of resistance genes (RGs). To investigate the impact of environmental stress on the disturbance of exogenous multidrug-resistant bacteria (mARB) within the indigenous microbiome and proliferation of RGs, an intestinal conjugative system was established to simulate the invasion of mARB into the intestinal microbiota in vitro. Oxytetracycline (OTC) and heavy metals (Zn, Cu, Pb), commonly encountered in aquaculture, were selected as typical stresses for investigation. Adenosine 5'-triphosphate (ATP), hydroxyl radical (OH·-) and extracellular polymeric substance (EPS) were measured to investigate their influence on the acceptance of RGs by intestinal bacteria. The results showed that the transfer and diffusion of RGs under typical combined stressors were greater than those under a single stressor. Combined effect of OTC and heavy metals (Zn, Cu) significantly increased the activity and extracellular EPS content of bacteria in the intestinal conjugative system, increasing intI3 and RG abundance. OTC induced a notable inhibitory response in Citrobacter and exerted the proportion of Citrobacter and Carnobacterium in microbiota. The introduction of stressors stimulates the proliferation and dissemination of RGs within the intestinal environment. These results enhance our comprehension of the typical stresses effect on the RGs dispersal in the intestine.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.