Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.

Objective: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. Methods: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 µL of bacterial solution at concentrations of 0, 0.1 and 0.2 g/15 mL, respectively. Results: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p < 0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae and Megasphaera (p < 0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body. Conclusion: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.

Evaluation of AlphaFold2 Structures for Hit Identification across Multiple Scenarios.

The introduction of AlphaFold2 (AF2) has sparked significant enthusiasm and generated extensive discussion within the scientific community, particularly among drug discovery researchers. Although previous studies have addressed the performance of AF2 structures in virtual screening (VS), a more comprehensive investigation is still necessary considering the paramount importance of structural accuracy in drug design. In this study, we evaluate the performance of AF2 structures in VS across three common drug discovery scenarios: targets with holo, apo, and AF2 structures; targets with only apo and AF2 structures; and targets exclusively with AF2 structures. We utilized both the traditional physics-based Glide and the deep-learning-based scoring function RTMscore to rank the compounds in the DUD-E, DEKOIS 2.0, and DECOY data sets. The results demonstrate that, overall, the performance of VS on AF2 structures is comparable to that on apo structures but notably inferior to that on holo structures across diverse scenarios. Moreover, when a target has solely AF2 structure, selecting the holo structure of the target from different subtypes within the same protein family produces comparable results with the AF2 structure for VS on the data set of the AF2 structures, and significantly better results than the AF2 structures on its own data set. This indicates that utilizing AF2 structures for docking-based VS may not yield most satisfactory outcomes, even when solely AF2 structures are available. Moreover, we rule out the possibility that the variations in VS performance between the binding pockets of AF2 and holo structures arise from the differences in their biological assembly composition.

The association between vitamin C intake and the risk of abdominal aortic calcification: A population-based study.

BACKGROUND: The beneficial effects of dietary vitamin C intake on human health have received widespread attention from the population. However, the correlation between vitamin C intake and abdominal aortic calcification remains unclear. The authors aimed to investigate the relationship between dietary vitamin C intake and AAC in US adults. METHODS: Our data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, and participants had complete data on dietary vitamin C intake and AAC scores. We used weighted multivariate linear regression and multivariate logistic regression analyses to explore the independent relationship between vitamin C intake and AAC scores, along with subgroup analyses and restricted cubic splines. RESULTS: A total of 2876 participants were enrolled in this study, with a mean AAC score of 1.47 ± 0.14 and a prevalence of severe AAC of 8.12%. We observed a 0.5 unit decrease in AAC scores in participants in the highest quartile compared to those in the lowest quartile of VitC intake. In contrast, there was no significant correlation between VitC intake and risk of severe AAC. Besides, subgroup analysis and interaction tests showed that there was no dependence of the association between VitC intake and AAC. CONCLUSION: Dietary VitC intake was associated with reduced AAC scores, but there was no significant correlation between dietary VitC intake and risk of severe AAC.

Axillary ultrasonography for early-stage invasive breast cancer.

BACKGROUND: Among women with early invasive breast cancer and 1-2 positive sentinel nodes, sentinel lymph node biopsy (SLNB) is non-inferior to axillary lymph node dissection (ALND).1-3 However, preoperative axillary ultrasonography (AxUS) may not be sensitive enough to discriminate burden of nodal metastasis in these patients, potentially leading to overtreatment.4-6 This study compares axillary operation rates in patients who did and did not receive preoperative AxUS, assessing its utility and risks for overtreatment. METHODS: This is a retrospective cohort study of patients with clinical T1/T2 breast tumors who were clinically node negative and underwent an axillary operation. RESULTS: Patients who had preoperative AxUS received more ALND compared to patients who did not (5.6% vs. 1.4%, p â€‹< â€‹0.001). There was no significant difference in the number of additional axillary operations following SLNB (2.1% vs. 2.3%, p â€‹= â€‹0.77). CONCLUSION: Eliminating preoperative AxUS is associated with fewer invasive ALND procedures, without increased rate of axillary reoperations.

The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system in M. marinum.

Bacterial pathogens use protein secretion systems to transport virulence factors and regulate gene expression. Among pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum, the ESAT-6 system 1 (ESX-1) secretion is crucial for host interaction. Secretion of protein substrates by the ESX-1 secretion system disrupts phagosomes, allowing mycobacteria cytoplasmic access during macrophage infections. Deletion or mutation of the ESX-1 system attenuates mycobacterial pathogens. Pathogenic mycobacteria respond to the presence or absence of the ESX-1 system in the cytoplasmic membrane by altering transcription. Under laboratory conditions, the EspM repressor and WhiB6 activator control transcription of specific ESX-1-responsive genes, including the ESX-1 substrate genes. However, deleting the espM or whiB6 gene does not phenocopy the deletion of the ESX-1 substrate genes during macrophage infection by M. marinum. In this study, we identified EspN, a critical transcription factor whose activity is masked by the EspM repressor under laboratory conditions. In the absence of EspM, EspN activates transcription of whiB6 and ESX-1 genes during both laboratory growth and macrophage infection. EspN is also independently required for M. marinum growth within and cytolysis of macrophages, similar to the ESX-1 genes, and for disease burden in a zebrafish larval model of infection. These findings suggest that EspN and EspM coordinate to counterbalance the regulation of the ESX-1 system and support mycobacterial pathogenesis.IMPORTANCEPathogenic mycobacteria, which are responsible for tuberculosis and other long-term diseases, use the ESX-1 system to transport proteins that control the host response to infection and promote bacterial survival. In this study, we identify an undescribed transcription factor that controls the expression of ESX-1 genes and is required for both macrophage and animal infection. However, this transcription factor is not the primary regulator of ESX-1 genes under standard laboratory conditions. These findings identify a critical transcription factor that likely controls expression of a major virulence pathway during infection, but whose effect is not detectable with standard laboratory strains and growth conditions.

Psychological status of residents at the onset of nationwide COVID-19 lockdown in low- and medium-risk areas of China.

The coronavirus disease 2019 (COVID-19), a dual threat to public physical and mental health, prompted an investigation into the psychological well-being of residents in low- to medium-risk areas of China during the initial stages of the pandemic. We administered WeChat-based questionnaire surveys and employed chi-square tests and multiple logistic regression to analyze correlations between residents' age, gender, education, symptoms, COVID-19 close contact history, information sources, and anxiety, depression, and attitudes toward lockdown measures. We received 10,433 valid questionnaires, revealing 26% anxiety and 19.5% depression. Support for lockdown measures reached 98.2%. Factors such as female gender, self-diagnosed pneumonia symptoms, close contact history, and higher education levels increased anxiety risk. Having a doctorate posed a severe anxiety risk, at 4.5 times (P = .019, 95% CI 1.29-15.73). Older age acted as a protective factor, reducing severe anxiety risk to 0.98 and 0.22 times (P < .001, 95% CI 0.14-0.34). Females with a master degree or below and those receiving COVID-19 information from multiple channels faced higher depression risk. Pneumonia symptoms were a risk for all anxiety and depression degrees. Attitudes toward lockdown measures had no significant impact on psychological status, nor did any of the analyzed factors affect residents' overall attitude toward lockdown. Our findings underscore the need for increased psychological counseling, particularly for young females with lower educational backgrounds or self-suspected infection symptoms, to mitigate mild to moderate anxiety and depression in future epidemics or pandemics. The public, especially those of working age with doctorates or higher education, bears the highest risk of severe anxiety. Lockdown measures enjoy strong support in low- to medium-risk areas of China.

DTTZ suppresses ferroptosis and reverses mitochondrial dysfunction in normal tissues affected by chemotherapy.

Conventional antineoplastic therapies cause severe normal tissue damage and existing cytoprotectants with acute toxicities or potential tumor protection limit their clinical application. We evaluated the selective cytoprotection of 2,2-dimethylthiazolidine hydrochloride in this study, which could protect normal tissue toxicity without interfering antineoplastic therapies. By using diverse cell lines and A549 xenograft model, we discovered a synthetic aminothiol 2,2-dimethylthiazolidine hydrochloride selectively diminished normal cellular ferroptosis via SystemXc-/Glutathione Peroxidase 4 pathway upon antineoplastic therapies without interfering the anticancer efficacy. We revealed the malignant and non-malignant tissues presenting different energy metabolism patterns. And cisplatin induces disparate replicative stress, contributing to the distinguishable cytoprotection of 2,2-dimethylthiazolidine in normal and tumor cells. The compound pre-application could mitigate cisplatin-induced normal cellular mitochondrial oxidative phosphorylation (OXPHOS) dysfunction. Pharmacologic ablation of mitochondria reversed 2,2-dimethylthiazolidine chemoprotection against cisplatin in the normal cell line. Combined, these results provide a potential therapeutic adjuvant to selectively diminish normal tissue damages retaining antineoplastic efficacy.

Inhibition of PI3K/AKT signaling pathway prevents blood-induced heterotopic ossification of the injured tendon.

Objective: It is a common clinical phenomenon that blood infiltrates into the injured tendon caused by sports injuries, accidental injuries, and surgery. However, the role of blood infiltration into the injured tendon has not been investigated. Methods: A blood-induced rat model was established and the impact of blood infiltration on inflammation and HO of the injured tendon was assessed. Cell adhesion, viability, apoptosis, and gene expression were measured to evaluate the effect of blood treatment on tendon stem/progenitor cells (TSPCs). Then RNA-seq was used to assess transcriptomic changes in tendons in a blood infiltration environment. At last, the small molecule drug PI3K inhibitor LY294002 was used for in vivo and in vitro HO treatment. Results: Blood caused acute inflammation in the short term and more severe HO in the long term. Then we found that blood treatment increased cell apoptosis and decreased cell adhesion and tenonic gene expression of TSPCs. Furthermore, blood treatment promoted osteochondrogenic differentiation of TSPCs. Next, we used RNA-seq to find that the PI3K/AKT signaling pathway was activated in blood-treated tendon tissues. By inhibiting PI3K with a small molecule drug LY294002, the expression of osteochondrogenic genes was markedly downregulated while the expression of tenonic genes was significantly upregulated. At last, we also found that LY294002 treatment significantly reduced the tendon HO in the rat blood-induced model. Conclusion: Our findings indicate that the upregulated PI3K/AKT signaling pathway is implicated in the aggravation of tendon HO. Therefore, inhibitors targeting the PI3K/AKT pathway would be a promising approach to treat blood-induced tendon HO.

Optimization of Fermented Maize Stover for the Fattening Phase of Geese: Effect on Production Performance and Gut Microflora.

To optimize the utilization of fermented maize stover (FMS) feed during the fattening phase of Xianghai flying geese (XFG), a total of 300 XFG at 125 days of age were randomly assigned to four dietary treatment groups with three replicates of 25 in each set. Group A was fed the basal fattening diet, while the B, C, and D groups were fed the basic fattening diet and diets supplemented with 5%, 10% or 15% FMS, respectively. The findings indicate that the production performance indicators (especially the dressed, eviscerated and breast muscle yield) of Group D closely resembled Group A more than Groups B and C. Intestinal morphometry found that the jejunal villus height and the villus height/crypt depth were significantly increased in Group D compared to Group A. Next, 16S rRNA amplicon sequencing of the extracted DNA revealed that beneficial microbiota (Coprococcus and Victivallis) showed increased abundance in Group D. Cecal flora function analysis further revealed that some amino acid and glycerol biosynthesis were found to be associated with growth performance in geese. These findings suggest that incorporating 15% FMS as a substitute for a portion of the feed during the fattening phase of XFG can effectively sustain their production performance, optimize the gut microbial community and morphometrical traits, provide new insight into using non-conventional feed resources to reduce feed cost and improve economic benefits in the breeding industry.

Enhancing the photodynamic effect of curcumin through modification with TiO2 nanoparticles and cationic polymers.

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO2) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO2-CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption. Cellular uptake efficiency of TCS was also enhanced, and it demonstrated nearly 4.7-fold higher reactive oxygen species (ROS) generation than CUR. Furthermore, TCS displayed the ability to attach to the cell membrane and enter cells within a 30-min incubation period. Upon irradiation, TCS exhibited remarkable cytotoxicity, resulting in a significant reduction in the viability of various cancer cells. Autofluorescence lifetime imaging of intracellular reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) enzymes indicated that cancer cells treated with TCS and irradiation undergo a metabolic pathway shift from oxidative phosphorylation to glycolysis. These findings highlight the potential of TCS as an effective PDT agent for cancer treatment.

Synergistic effect of combating air pollutants and carbon emissions in the Yangtze River Delta of China: spatial and temporal divergence analysis and key influencing factors.

Synergizing the reduction of air pollutants and carbon emissions (APCE) has become a critical tactic alternative to address the issue of climate change. Taking the Yangtze River Delta (YRD) region of China as a case study, this paper explores the spatial and temporal distribution pattern of the coupling coordination degree (CCD) of combating APCE from 2011 to 2022, analyzes the dynamic change in CCD using the convergence test, and investigates the key factors affecting CCD via the Tobit regression model. The results show that (1) from 2011 to 2022, the air pollutants (AP) and CO2 emission (CE) in the YRD region decrease at the annual rate of 10.32% and 0.85%, respectively; (2) the CCD of reducing APCE in the YRD presents a W-shaped fluctuation before 2016 and then steps into a steady increase status after 2016; (3) the order of CCD in four provincial-level units by 2022 is Shanghai > Zhejiang > Jiangsu > Anhui. The proportion of cities where the CCD of reducing APCE enters the high-coordination period has reached 87.8%; and (4) the Tobit regression results affirm that economic growth, industrial structure, and green technological innovation exacerbate the CCD of combating APCE, while opening-up level mitigates it. The findings offer policymakers valuable insights into the importance of pursuing collaborative governance over APCE and ensuring sustainable development.

Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats.

OBJECTIVE: Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. METHODS: Forty male Sprague-Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. RESULTS: TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.001), Cre (z = 3.476; P < 0.001), CysC (z = 4.052; P < 0.001), NGAL (z = 3.661; P < 0.001), and CRP (z = 5.286; P < 0.001) gradually increased after uranium exposure, whereas TAS (z = -3.823; P < 0.001), tissue U (z = -2.736; P = 0.001), Hcy (z = -2.794; P = 0.005), and Lp-PLA2 (z = -4.515; P < 0.001) gradually decreased. The serum U level showed a V-shape change (z = -1.655; P = 0.094). The uranium levels in the kidney tissue and serum were positively correlated with TOS (r = 0.440 and 0.424; P = 0.005 and 0.007) and OSI (r = 0.389 and 0.449; P = 0.013 and 0.004); however, serum U levels were negatively correlated with TAS (r = -0.349; P = 0.027). Partial correlation analysis revealed that NGAL was closely correlated to tissue U (rpartial = 0.455; P = 0.003), CysC was closely correlated to serum U (rpartial = 0.501; P = 0.001), and Lp-PLA2 was closely correlated to TOS (rpartial = 0.391; P = 0.014), TAS (rpartial = 0.569; P < 0.001), and OSI (rpartial = -0.494; P = 0.001). Pearson correlation analysis indicated that the Hcy levels were negatively correlated with tissue U (r = -0.344; P = 0.030) and positively correlated with TAS (r = 0.396; P = 0.011). CONCLUSION: The uranium-induced oxidative injury may be mainly reflected in enhanced endothelial inflammation, and the direct chemical toxicity of uranium plays an important role in the process of kidney injury, especially in renal tubular injury. In addition, CysC may be a sensitive marker reflecting the nephrotoxicity of uranium; however, Hcy is not suitable for evaluating short-term endothelial inflammation involving oxidative stress.

The relationship between circulating metabolites and prostate hyperplasia: a Mendelian randomization study.

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.

Anomalous coarsening of coalescing nucleoli in human cells.

Coarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium-as an increase in droplet size lowers the system's free energy-however, coarsening of droplets in nonequilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coalescing with each other. Upon coarsening, human nucleoli exhibit an anomalous volume distribution P(V)∼V-1, which cannot be explained by any existing theory. In this work, we investigate physical mechanisms behind the anomalous coarsening of human nucleoli. Using spinning disk confocal microscopy, we simultaneously record dynamic behavior of nucleoli and their surrounding chromatin before their coalescence in live human cells. We find that nucleolar anomalous coarsening persists during the entire cell cycle. We measure chromatin flows and density between and around nucleoli, as well as relative motion of two nucleoli before they coalesce. We find that, before nucleolar coalescence, chromatin concentration decreases in the space between nucleoli and the nucleoli move faster toward each other, resembling an effective depletion attraction between the coalescing nucleoli. Indeed, our computational simulations of nucleolar dynamics show that short-ranged attraction is sufficient to explain the observed anomalous volume distribution of human nucleoli. Overall, our results reveal a potential physical mechanism contributing to coarsening of human nucleoli. Such knowledge expands our picture of the physical behavior of liquid condensates inside the cell nucleus and our understanding of the dynamic nuclear organization.

Integrated analysis of whole genome and transcriptome sequencing uncovers genetic differences between Zi goose and Xianghai flying goose.

Zi goose is a famous indigenous breed originating from northeast China with high annual egg production. Xianghai flying goose is a composite breed and is bred by crosses of the wild swan goose and the Zi goose. Our previous study revealed significant differences in muscle fiber characteristics between the two populations. Here, we aimed to reveal the underlying genetic basis of the above phenotype differences through whole-genome and transcriptome analysis. A total of 20 blood samples (10 Zi geese and 10 Xianghai flying geese) were used for whole genome sequencing, and eight breast muscle tissue samples (four Zi geese and four Xianghai flying geese) were used for RNA sequencing. Using the FST and XP-EHH analysis, some highly differentiated genome regions annotated with egg production (RORB, WNT4, BMPR1B) and breast muscle development (WNT7B) between the two populations were detected. RNA-sequencing analysis revealed differentially expressed genes related to muscle development (IGF1, PAX7). Moreover, several genes were detected by both genome and transcriptome analysis, and some of them were reported to be associated with muscle growth (SLIT2, PREX1) and intramuscular fat (COL6A1). These findings will help researchers better understand the genetic basis related to egg production and muscle development in geese.

Engineered platelet cell motors for boosted cancer radiosensitization.

Design of engineered cells to target and deliver nanodrugs to the hard-to-reach regions has become an exciting research area. However, the limited penetration and retention of cell-based carriers in tumor tissue restricted their therapeutic efficiency. Inspired by the enhanced delivery behavior of mobile micro/nanomotors, herein, urease-powered platelet cell motors (PLT@Au@Urease) capable of active locomotion, tumor targeting, and radiosensitizers delivery were designed for boosting radiosensitization. The engineered platelet cell motors were constructed by in situ synthesis and loading of radiosensitizers gold nanoparticles in platelets, and then conjugation with urease as the engine. Under physiological concentration of urea, thrust around PLT@Au@Urease motors can be generated via the biocatalytic reactions of urease, leading to rapid tumor cell targeting and enhanced cellular uptake of radiosensitizers. Encouragingly, in comparison with engineered PLT without propulsion capability (PLT@Au), the self-propelled PLT@Au@Urease motors could significantly increase intracellular ROS level and exacerbate nuclear DNA damage induced by γ-radiation, resulting in a remarkably high sensitization enhancement rate (1.89) than that of PLT@Au (1.08). In vivo experiments with 4 T1-bearing mice demonstrated that PLT@Au@Urease in combination with radiation therapy possessed good antitumor performance. Such an intelligent cell motor would provide a promising approach to enhance radiosensitization and broaden the applications of cell motor-based delivery systems.

Electrochemical C-N Bond Formation within Boron Imidazolate Cages Featuring Single Copper Sites.

Electrocatalysis expands the ability to generate industrially relevant chemicals locally and on-demand with intermittent renewable energy, thereby improving grid resiliency and reducing supply logistics. Herein, we report the feasibility of using molecular copper boron-imidazolate cages, BIF-29(Cu), to enable coupling between the electroreduction reaction of CO2 (CO2RR) with NO3- reduction (NO3RR) to produce urea with high selectivity of 68.5% and activity of 424 µA cm-2. Remarkably, BIF-29(Cu) is among the most selective systems for this multistep C-N coupling to-date, despite possessing isolated single-metal sites. The mechanism for C-N bond formation was probed with a combination of electrochemical analysis, in situ spectroscopy, and atomic-scale simulations. We found that NO3RR and CO2RR occur in tandem at separate copper sites with the most favorable C-N coupling pathway following the condensation between *CO and NH2OH to produce urea. This work highlights the utility of supramolecular metal-organic cages with atomically discrete active sites to enable highly efficient coupling reactions.

Construction and application of a nursing human resource allocation model based on the case mix index.

BACKGROUND: The case mix index (CMI) may reflect the severity of disease and the difficulty of care objectively, and is expected to be an ideal indicator for assessing the nursing workload. The purpose of this study was to explore the quantitative relationship between daily nursing worktime (DNW) and CMI to provide a method for the rational allocation of nursing human resources. METHODS: Two hundred and seventy-one inpatients and 36 nurses of the department of hepatobiliary surgery were prospectively included consecutively from August to September 2022. The DNW of each patient were accurately measured, and the CMI data of each patient were extracted. Among 10 curve estimations, the optimal quantitative model was selected for constructing the nursing human resource allocation model. Finally, the applicability of the allocation model was preliminarily assessed by analyzing the relationship between the relative gap in nursing human resources and patient satisfaction, as well as the incidence of adverse events in 17 clinical departments. RESULTS: The median (P25, P75) CMI of the 271 inpatients was 2.62 (0.92, 4.07), which varied by disease type (F = 3028.456, P < 0.001), but not by patient gender (F = 0.481, P = 0.488), age (F = 2.922, P = 0.089), or level of care (F = 0.096, P = 0.757). The median (P25, P75) direct and indirect DNW were 76.07 (57.98, 98.85) min and 43.42 (39.42, 46.72) min, respectively. Among the 10 bivariate models, the quadratic model established the optimal quantitative relationship between CMI and DNW; DNW = 92.3 + 4.8*CMI + 2.4*CMI2 (R2 = 0.627, F = 225.1, p < 0.001). The relative gap between theoretical and actual nurse staffing in the 17 clinical departments were linearly associated with both patient satisfaction (r = 0.653, P = 0.006) and incidence of adverse events (r = - 0.567, P = 0.021). However, after adjusting for other factors, it was partially correlated only with patient satisfaction (rpartial = 0.636, P = 0.026). CONCLUSION: The DNW derived from CMI can be used to allocate nursing human resources in a rational and convenient way, improving patient satisfaction while ensuring quality and safety.

C3-epi-25(OH)D3 percentage, not level, may be a potential biomarker to reflect its pathological increase in multiple diseases: a cross-sectional case-control study.

National surveys in developed countries have examined the presence of C3-epimer of 25-hydroxyvitamin D3 [C3-epi-25(OH)D3]. However, controversy remains regarding its association with disease occurrence due to its high correlation with 25-hydroxyvitamin D3 [25(OH)D3]. This study aims to investigate whether %C3-epi-25(OH)D3 can serve as an indicator for this relationship with various diseases. A total of 3086 healthy participants and 4120 patients were included in this study. We investigated the association between C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels with gender, age, and season; compared the performance of C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 across different disease conditions; and explored the correlation between %C3-epi-25(OH)D3 and various diseases. Results indicated that C3-epi-25(OH)D3 varied significantly by gender, age, and season (z/χ2 = 3.765, 10.163, and 150.975, all P < 0.01), while only season for %C3-epi-25(OH)D3 (χ2 = 233.098, P < 0.001). In contrast to the significant decrease in C3-epi-25(OH)D3, %C3-epi-25(OH)D3 showed a significant increase in 8 out of 11 disease categories (z = 3.464 ~ 11.543, all Padj < 0.05). Similar opposite changes were also observed in most of the investigated 32 specific diseases. Moreover, an elevation in %C3-epi-25(OH)D3 was found to be significantly associated with 29 specific diseases both in univariate analysis (OR = 1.16 ~ 2.10, all P < 0.05) and after adjusting for gender, age, and season (OR = 1.15 ~ 1.50, all P < 0.05). However, after further adjustment for 25(OH)D3 levels, the association remained significant only for 15 specific diseases (OR = 1.11 ~ 1.50, all P < 0.05). Seasonal stratification analysis further supports the consistent association of %C3-epi-25(OH)D3 with disease across all or nearly all four seasons. In conclusion, %C3-epi-25(OH)D3 may better reflect the production of C3-epi-25(OH)D3 in disease conditions, thereby offering a more applicable approach to investigate its association with diseases. However, the interpretation of this relationship may be confounded by 25(OH)D3 as a potential covariate.