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Abstract Background The triglyceride glucose (TyG) index, defined as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], provides insights into overall metabolic status. However, the association between the TyG index and gout has not been investigated. Therefore, this study explored the correlation between the TyG index and gout. Methods Using data from the National Health and Nutrition Examination Survey, which was conducted from 2007 to 2018, this study investigated the relationship between the TyG index and gout. Demographic data and potential risk factors were analyzed and compared using t tests for continuous data and chi-square tests for categorical data. Logistic regression and subgroup analysis were performed to examine the association between the TyG index and gout. Results A total of 14,924 participants were enrolled, among whom 726 (4.86%) were diagnosed with gout. Without controlling for any covariates, a significant positive correlation was observed between an elevated TyG index and increased risk of gout, with an odds ratio (OR) of 2.07 and a 95% confidence interval (CI) ranging from 1.76 to 2.43. After full adjustment, this association remained statistically significant, with an adjusted OR of 1.43 and a 95% CI from 1.14 to 1.80. Subgroup analyses revealed significant interactions, particularly for females (OR = 2.55; 95% CI: 2.00-3.26), individuals with no military service history (OR = 2.15; 95% CI: 1.66–2.43), and those without diabetes (OR = 2.00; 95% CI: 1.64–2.43). Conclusion A positive correlation was observed between the TyG index and gout. Consequently, further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in gout.

This case report details the challenging management of a 45-year-old male construction worker who suffered severe multiple injuries after a fall and subsequent collision with cement mixers. The patient presented with extensive injuries, including amputation, fractures and internal bleeding, leading to a state known as the ‘triangle of death’. Despite the initial grim prognosis, evidenced by an ISS score of 28 and a mortality risk coefficient of 89.56%, the patient was successfully resuscitated and managed through a multidisciplinary approach. This included damage control resuscitation, emergency vascular interventions and targeted temperature management for brain protection. The patient’s recovery highlights the effectiveness of comprehensive trauma management and the critical role of coordinated care in severe multi-trauma cases.

ObjectiveTo compare the therapeutic efficacy of robot-assisted and manual screw placement techniques for the treatment of pelvic fractures.MethodsThis study included patients with pelvic fractures admitted to our orthopedic department between January 2020 and January 2022. They were randomly assigned to either the robot-assisted group or the control group. Various parameters, including surgical duration, intraoperative bleeding, fluoroscopy frequency, postoperative pain, length of hospitalization, postoperative hematological indices, postoperative functional scores, and postoperative complications, were compared between the two groups.ResultsThere were no significant differences in age, sex, body mass index, and preoperative hematological parameters between the two groups. The robot-assisted group exhibited significantly shorter surgical duration, lower fluoroscopy frequencies, lower postoperative pain scores, and shorter length of hospitalization compared to the control group. At 3 and 6 months postoperatively, patients in the robot-assisted group demonstrated significantly higher Majeed functional scores in comparison to the control group. However, there were no significant differences in Majeed scores at 12 months postoperatively. Moreover, there were no significant differences in postoperative complications between the two groups.ConclusionRobot-assisted minimally invasive treatment of pelvic fractures using hollow screws effectively reduced surgical duration, mitigated intraoperative bleeding and postoperative pain, shortened hospital stays, and promoted faster functional recovery.

Abstract Background Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). Case presentation Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. Conclusion Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. Suitable for people with Infectious Diseases; Neonatology; Obstetrics.

Objectives: In China, primary healthcare (PHC) facilities have high antibiotic prescribing rates for upper respiratory tract infections (URTIs), which are primarily viral and self-limited. This study aimed to identify the main factors influencing PHC physicians’ antibiotic decisions for URITs based on the theory of planned behavior. Methods: A convergent mixed-methods study was conducted at 30 PHC facilities across Shaanxi Province, China. A total of 108 PHC physicians completed a five-point Likert Scale questionnaire focused on behavioral components of antibiotic prescribing, including attitudes, subjective norms, perceived behavioral control, belief in past experiences, and prescribing intentions. Twenty-two physicians participated in semi-structured interviews. Results: Respondents had a good awareness of AMR (Mean = 4.49) and a weak belief regarding the benefit of antibiotics (Mean = 2.34). The mean score for subjective norms was 3.36, and respondents had good control over their prescribing behavior (Mean = 4.00). A reliance on past prescribing experiences was observed (Mean = 3.34), and physicians’ antibiotic prescribing intention was 3.40 on average. Multiple linear regression revealed that physicians showing a more favorable attitude towards antibiotics (p = 0.042) and relying more on their past experiences (p = 0.039) had a higher antibiotic prescribing intention. Qualitative interviews indicated that most physicians would consider prescribing antibiotics when facing diagnostic uncertainty. Low utilization of diagnostic tests, limited effectiveness of training programs, inadequate knowledge of guidelines, and lack of feedback on antibiotic prescriptions all contributed to antibiotic overprescribing. Conclusions: PHC physicians in China demonstrated strong intentions to prescribe antibiotics for URTIs when facing diagnostic uncertainty. Beliefs about antibiotics and previous prescribing behavior were significantly linked to prescribing intentions. Multifaceted interventions that focus on facilitating diagnostic tests, improving the quality of training, effectively implementing clinical guidelines, and providing practical feedback on antibiotic prescriptions may help reduce antibiotic overprescribing in China’s PHC facilities.

Objectives: Overuse of antibiotics in healthcare remains prevalent and requires urgent attention in China, particularly in primary healthcare (PHC) facilities. This study aimed to describe the patterns of antibiotic prescriptions for acute upper respiratory tract infections (URTIs) in PHC facilities in China and to investigate how PHC physicians’ knowledge influences their antibiotic prescribing behavior. Methods: A cross-sectional survey linking physician questionnaire responses and their prescription data was conducted in Shaanxi Province, China. The proportions of URTI visits that received at least one antibiotic, combined antibiotics, and broad-spectrum antibiotics were the main outcomes reflecting antibiotic prescribing behavior. Multivariate mixed-effects logistic regressions were applied to analyze the relationship between PHC physicians’ knowledge about antibiotics and their antibiotic prescribing behavior. Results: A total of 108 physicians filled out the questionnaires between February 2021 and July 2021, and a sample of 11,217 URTI visits attended by these physicians from 1 January 2020 to 31 December 2020 were included in the analysis. The overall mean score of our respondents on the knowledge questions was 5.2 (total score of 10). Over sixty percent (61.2%; IQR 50.2–72.1) of the URTI visits received antibiotics. The percentages of URTI visits prescribed with combined and broad-spectrum antibiotics were 7.8% (IQR 2.3–10.2) and 48.3% (IQR 36.7–58.7), respectively. Third-generation cephalosporins were the most frequently used antibiotics. Physicians with lower antibiotic knowledge scores were more inclined to prescribe antibiotics (p < 0.001), combined antibiotics (p = 0.001), and broad-spectrum antibiotics (p < 0.001). Conclusions: Physicians’ insufficient knowledge was significantly associated with antibiotic overprescribing. Professional training targeting physicians’ knowledge of antibiotics is urgently needed to improve the rational use of antibiotics in grassroots healthcare facilities in China.

Magnesium hydride (MgH2) has attracted considerable interest due to a number of favourable characteristics for hydrogen production via hydrolysis. In this study, MgH2-NaH composites with varying composition ratios were prepared by ball milling for different durations. The hydrogen production performances and enhancement mechanisms were subjected to meticulous investigation. The results revealed that the hydrogen production rate and kinetic properties of the composites were significantly improved with the rise in NaH content. For the MgH2-10 wt% NaH composites, the hydrogen production rate exhibited an initial increase followed by a subsequent decrease with the prolongation of ball milling. It is noteworthy that the hydrolysis of the composites in deionised water exhibited a significant improvement in reaction kinetics even after a mere 1 h of ball milling, releasing 1119 mL g−1 of hydrogen in 30 s, with a conversion rate of 69.2%. The highest hydrolysis hydrogen generation rate of the 10 h milled MgH2-10 wt% NaH composite in deionised water at 30 °C was 1360 mL g−1, with a hydrogen conversion rate of 83.7% and a hydrolysis activation energy of 17.79 kJ mol−1. The notable improvement in the hydrolysis performance of the MgH2-NaH composite is attributed to the rapid generation of high temperatures at the interface, resulting from the exothermic reaction of sodium hydride hydrolysis.

Vegetation to some extent can reflect the overall state of the ecological environment, and increasing vegetation cover can improve the quality of the ecological environment. The southwest karst region of China is a typical ecologically fragile area and an important ecological barrier. Against the backdrop of intensified human activities, the vegetation dynamics in the karst region have attracted widespread attention. Analyzing vegetation cover changes and their responses to human activities is important for regional ecological development. This study is based on SPOT-VGT NDVI data from 1998 to 2020 and employs trend analysis, “baseline” determination, multiple regression, residual analysis, and principal component analysis to investigate the characteristics of vegetation cover changes in the southwest karst region of China. Additionally, it quantifies the specific impacts of various human activities on these changes. The research findings indicate that (1) over the past 23 years, the interannual variability and seasonal differences in the NDVI of the southwest karst region have been significant, exhibiting an overall increasing trend. Spatially, the vegetation in this region demonstrates a decreasing trend from south to north and southwest to northeast. (2) Over time, the areas where vegetation has improved gradually expand, and the effectiveness of vegetation restoration increases with time. (3) Overall, human activities influence vegetation growth in the southwest karst landscape region of China. (4) The socioeconomic factors affecting vegetation cover changes in the southwest karst region of China primarily include economic development level, population and labor migration, urbanization development, and vegetation construction. These results provide a scientific basis for formulating reasonable ecological environment protection strategies by humans.

Reduced fertilizer efficiency caused by excessive use of nitrogen (N) fertilizer is a major problem in agriculture and a hot topic of research. Most studies have focused on the effect of N application rate on N efficiency, whereas there are limited studies on changing the N form to improve N yield and efficiency. Here, the effects of different N application rates and nitrate-to-ammonium N ratios on post-anthesis carbon (C) and N metabolism and maize yield under shallow-buried drip irrigation were investigated. Two rates of N application (210 kg·ha−1 (NA1) and 300 kg·ha−1 (NA2)) and three nitrate-to-ammonium N ratios (2:1 (NF1), 3:1 (NF2), and 4:1 (NF3)) were utilized. Post-anthesis photosynthetic characteristics, activities of key enzymes in photosynthetic C and N metabolism, nonstructural carbohydrate content, post-anthesis N accumulation and transportation, yield, and N-use efficiency were determined. At both N application rates, NF2 treatment enhanced photosynthetic activity in the ear-leaf at silking stage and promoted key enzyme activities of C and N metabolic pathways, compared with NF1 and NF3. Furthermore, NF2 significantly increased nonstructural carbohydrate accumulation (4.00–64.71%), post-anthesis N accumulation and transportation (11.00–38.00%), and grain yield (2.60–13.08%). No significant differences between NA1 and NA2 were observed under NF2 in most of the measured variables; however, NA1 had higher N-use efficiency. Thus, the optimal treatment under shallow-buried drip irrigation was a N application rate of 210 kg ha−1 and a nitrate-to-ammonium N ratio of 3:1. These findings provide theoretical guidance on appropriate N applications for high-yield maize production.

In order to explore the suitability of Baijiu made from different Guizhou He varieties and establish its evaluation system. The 88 Guizhou He varieties were selected to brew the Baijiu, and their quality indexes were determined and analyzed to investigate the difference of quality indexes of Baijiu made from different Guizhou He varieties. At the same time, the brewing suitability quality of different Guizhou He varieties was comprehensively evaluated by principal component analysis, a two-dimensional analysis and cluster analysis, and the quality evaluation model of which was established. The results showed that there were significant differences in quality indexes of Baijiu made from different varieties of Guizhou He (P

Abstract Keratinocytes are closely associated with innate immunity and inflammatory responses, and are dysregulated during the development of psoriasis, but the underlying mechanisms are not yet fully understood. This work aims to reveal the effects of long non-coding RNA (lncRNA) UCA1 in psoriatic keratinocytes. UCA1 was identified as a psoriasis-related lncRNA that highly expressed in psoriatic lesions. The transcriptome and proteome data of keratinocyte cell line HaCaT showed that UCA1 could positively regulate inflammatory functions, such as response to cytokine. Furthermore, UCA1 silencing decreased inflammatory cytokine secretion and innate immunity gene expression in HaCaT, its culture supernatant also decreased the migration and tube formation ability of vascular endothelial cells (HUVECs). Mechanistically, UCA1 activated the NF-κB signaling pathway, which is regulated by HIF-1α and STAT3. We also observed a direct interaction between UCA1 and N6-methyladenosine (m6A) methyltransferase METTL14. Knocking down METTL14 counteracted the effects of UCA1 silencing, indicating that it can suppress inflammation. In addition, the levels of m6A-modified HIF-1α were decreased in psoriatic lesions, indicating that HIF-1α is a potential target of METTL14. Taken together, this work indicates that UCA1 positively regulates keratinocyte-driven inflammation and psoriasis development by binding to METTL14, and activating HIF-1α and NF-κB signaling pathway. Our findings provide new insights into the molecular mechanisms of keratinocyte-driven inflammation in psoriasis.

IntroductionCaries are at the forefront of childhood diseases. Although childhood caries is usually not life-threatening, it can affect children's dental–maxillofacial development and mental health and place significant financial and psychological burdens on parents. As the focus of childhood dental caries shifts to early diagnosis and prevention rather than restorative dentistry alone, screening children at a high risk of dental caries is urgent. Appropriate caries prevention measures and treatment sequences can effectively reduce the occurrence and development of dental caries in children.CaseWe report the case of a 7-year-old boy presenting with a high risk of dental caries involving multiple primary teeth and premature eruption of the permanent teeth. We shifted the caries status of the child from high to moderate likelihood. At the 9-month post-treatment follow-up, the patient had no new dental caries, and the length and width of the dental arch were effectively maintained.ConclusionOral health education, dental plaque removal in a regular basis, and fluoride application contribute to caries management.

Ultra-wideband (UWB) is a carrier-less communication technology that transmits data using narrow pulses of non-sine waves on the nanosecond scale. The UWB positioning system uses the multi-lateral positioning algorithm to accurately locate the target, and the positioning accuracy is seriously affected by the non-line-of-sight (NLOS) error. The existing non-line-of-sight error compensation methods lack multidimensional consideration. To combine the advantages of various methods, a two-stage UWB-INS fusion localization algorithm is proposed. In the first stage, an NLOS signal filter is designed based on support vector machines (SVM). In the second stage, the results of UWB and Inertial Navigation System (INS) are fused based on Kalman filter algorithm. The two-stage fusion localization algorithm achieves a great improvement on positioning system, it can improve the localization accuracy by 79.8% in the NLOS environment and by 36% in the (line-of-sight) LOS environment.

Recent innovations in business models and technology have brought out new mobility systems, including shared and electric micro-mobility. A rapidly expanding strand of literature mirrors the micro-mobility’s exponential growth and popularity. While many studies analyze micro-mobility from operations, management and user perspectives, fewer works investigate the micro-mobility and built environment (BE) relationship. This paper systematically reviews the descriptive and empirical studies that investigate this relationship. It analyzes whether, similar to other transportation modes, micro-mobility (e.g., bike-sharing schemes and e-bikes/e-scooters) can potentially influence three BE aspects: urban design, land use, and transportation system. Furthermore, it outlines the recommended changes in the BE to support the micro-mobility and/or enhance the quality of the environment for non-users. This paper investigates the BE and micro-mobility relation at the three levels of node (e.g., the emergence of docking stations and parking stops), link (e.g., the street-level conflicts with walking/cycling/vehicle lanes) and network (e.g., infrastructure network creation and catchment area shifts). In addition, this relation is explored over time, based on the development stage of micro-mobility, the BE aspect (urban design, land use, or transport system), and spatial context (urban or rural). The findings are relevant for urban and transport planners, designers, researchers, policy makers and public authorities. They contribute to a much-needed evidence base for effective design and policy recommendations to accommodate micro-mobility in the BE to achieve a safe and inclusive public space.

The deformation characteristics of the cemented tailings backfill (CTB) has a significant influence on the stability of mine stope and surface subsidence after filling mining. An uniaxial compression experiment of the CTB containing different cement-tailings ratios (c/t) has been performed and it shows that the CTB has an obvious compaction hardening in the initial compaction stage and strain softening at the plastic yield stage. However, these nonlinear deformation characteristics of CTB are not fully understood in the previous studies. In this research, considering the nonlinear deformation characteristics, a complete constitutive model was proposed for the CTB based on the experimental stress–strain curves. This constitutive model has been programmed into FLAC3D to obtain the law of surface subsidence and assess the safety of the concentrator if the backfill method is adopted. In addition, a physical model experiment of filling mining is also carried out at the same condition. The results of these two simulation experiments show that the surface subsidence is negatively correlated with the distance between the concentrator and the collapse pit, and the maximum subsidence is less than 90 mm. Therefore, the filling mining method can effectively guarantee the safety of concentrator. This study provides a better understanding of the deformation characteristics of CTB and it also contributes to the underground filling technology of using CTB.

Summary: Global warming and rising temperature significantly increase the incidence of heat stress, which is known to affect the process of inflammation and aging. However, the effect of heat stress on skin melanogenesis is not fully known. We found that healthy foreskin tissues underwent significant pigmentation when exposed to 41°C. Furthermore, heat stress promoted melanogenesis in pigment cells by increasing the paracrine effects of keratinocytes. High-throughput RNA sequencing showed that heat stress activates the Hedgehog (Hh) signaling pathway in keratinocytes. The agonists of Hh signaling promote the paracrine effect of keratinocytes on melanogenesis. In addition, transient receptor potential vanilloid (TRPV) 3 agonists activate the Hh signaling in keratinocytes and augment its paracrine effect on melanogenesis. The heat-induced activation of Hh signaling is dependent on TRPV3-mediated Ca2+ influx. Heat exposure promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway. Our findings provide insights into the mechanisms of heat-induced skin pigmentation.

Abstract There are few reports on the material transformation and dominant microorganisms in the process of greening waste (GW) composting. In this study, the target microbial community succession and material transformation were studied in GW composting by using MiSeq sequencing and PICRUSt tools. The results showed that the composting process could be divided into four phases. Each phase of the composting appeared in turn and was unable to jump. In the calefactive phase, microorganisms decompose small molecular organics such as FA to accelerate the arrival of the thermophilic phase. In the thermophilic phase, thermophilic microorganisms decompose HA and lignocellulose to produce FA. While in the cooling phase, microorganisms degrade HA and FA for growth and reproduction. In the maturation phase, microorganisms synthesize humus using FA, amino acid and lignin nuclei as precursors. In the four phases of the composting, different representative genera of bacteria and fungi were detected. Streptomyces, Myceliophthora and Aspergillus, maintained high abundance in all phases of the compost. Correlation analysis indicated that bacteria, actinomycetes and fungi had synergistic effect on the degradation of lignocellulose. Therefore, it can accelerate the compost process by maintaining the thermophilic phase and adding a certain amount of FA in the maturation phase.

Abstract Background Most severe, critical, or mortal COVID-19 cases often had a relatively stable period before their status worsened. We developed a deterioration risk model of COVID-19 (DRM-COVID-19) to predict exacerbation risk and optimize disease management on admission. Method We conducted a multicenter retrospective cohort study with 239 confirmed symptomatic COVID-19 patients. A combination of the least absolute shrinkage and selection operator (LASSO), change-in-estimate (CIE) screened out independent risk factors for the multivariate logistic regression model (DRM-COVID-19) from 44 variables, including epidemiological, demographic, clinical, and lung CT features. The compound study endpoint was progression to severe, critical, or mortal status. Additionally, the model's performance was evaluated for discrimination, accuracy, calibration, and clinical utility, through internal validation using bootstrap resampling (1000 times). We used a nomogram and a network platform for model visualization. Results In the cohort study, 62 cases reached the compound endpoint, including 42 severe, 18 critical, and two mortal cases. DRM-COVID-19 included six factors: dyspnea [odds ratio (OR) 4.89;confidence interval (95% CI) 1.53–15.80], incubation period (OR 0.83; 95% CI 0.68–0.99), number of comorbidities (OR 1.76; 95% CI 1.03–3.05), D-dimer (OR 7.05; 95% CI, 1.35–45.7), C-reactive protein (OR 1.06; 95% CI 1.02–1.1), and semi-quantitative CT score (OR 1.50; 95% CI 1.27–1.82). The model showed good fitting (Hosmer–Lemeshow goodness, X2(8) = 7.0194, P = 0.53), high discrimination (the area under the receiver operating characteristic curve, AUROC, 0.971; 95% CI, 0.949–0.992), precision (Brier score = 0.051) as well as excellent calibration and clinical benefits. The precision-recall (PR) curve showed excellent classification performance of the model (AUCPR = 0.934). We prepared a nomogram and a freely available online prediction platform ( https://deterioration-risk-model-of-covid-19.shinyapps.io/DRMapp/ ). Conclusion We developed a predictive model, which includes the including incubation period along with clinical and lung CT features. The model presented satisfactory prediction and discrimination performance for COVID-19 patients who might progress from mild or moderate to severe or critical on admission, improving the clinical prognosis and optimizing the medical resources.

In the numerical simulation of site seismic responses, traditional equivalent linearization methods typically realized in the frequency domain cannot satisfactorily analyze the high-degree non-linearity of soil under strong input motions. Therefore, the “true” non-linear numerical methods performed in the time domain are often utilized in such cases. However, a crucial element of the time-domain non-linear method, which is the hysteresis model of soil that describes the rule controlling the loading–unloading behavior of soil, has no established guidelines for earthquake engineering. Different researchers presented different models, revealing the epistemic uncertainty related to the dynamic properties of soil. Thus, the time-domain non-linear method should consider this uncertainty in practice. Therefore, in this study, a one-dimensional (1D) time-domain non-linear site seismic response analysis program was developed. The developed program was coded using Fortran95 and integrates two kinds of soil hysteresis models (i.e., extended Masing model and dynamic skeleton curve model). In both models, the damping correction was introduced to calibrate the hysteresis loop area toward the damping ratio measured in the dynamic triaxial test or resonant column test. Moreover, the temporospatial finite difference algorithm was used to resolve the 1D non-linear wave equation, and its precision was demonstrated in comparison with the results of the frequency-domain program for the linear case. Finally, the non-linear seismic response of a specific site was calculated by the proposed program. The findings of the fitting were compared to those of the two popular time-domain non-linear programs DEEPSOIL (Hashash, V6.1) and CHARSOIL (Streeter et al., CHARSOIL, Characteristics Method Applied to Soils, 1974 March 25). Simultaneously, the Japanese KIK-net strong motion observation station data were applied to validate the reliability of this program.

PurposeTo evaluate the clinical effects of deep anterior lamellar keratoplasty (DALK) using a single graft after thermokeratoplasty assisted epikeratophakia for the treatment of acute corneal hydrops.MethodsThis novel surgical procedure was performed on seven eyes of seven patients between 2019 and 2020. The procedure combines a first-stage surgery of thermokeratoplasty assisted epikeratophkia with intracameral sterile air injection and a second-stage surgery of DALK using the same corneal graft for both procedures. Main outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and anterior segment optical coherence tomography (AS-OCT) parameters. Corneal transparency, epithelization, and the presence of neovascularization, were evaluated at the 1-year follow-up visit.ResultsCorneal edema resolved rapidly in six of the seven cases. The mean central corneal thickness was significantly reduced from baseline to 1 day, 1 week, 1 month, and 2 months after the first-stage surgery (P < 0.0001). At a mean of 2.1 ± 0.7 months after the first-stage surgery, DALK was successfully performed in all cases. Six months later, the mean central corneal thickness was 611 ± 31 μm and the mean thickness of the recipient’s residual stroma bed was 20 ± 6 μm at the central corneal area. Mean LogMAR CDVA improved from 1.74 ± 0.34 at baseline to 0.20 ± 0.11 after DALK (P < 0.0001). No postoperative complications appeared in our case series during the 1-year observation period.ConclusionVery good visual results were obtained with a novel technique (thermokeratoplasty assisted epikeratophakia followed by DALK using the same corneal graft) in the treatment of acute corneal hydrops.

The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.

Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response.Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor–ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing.Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor–ligand pairs.Conclusion: BLCA patients with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA.

Abstract By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient‐derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth. Investigating the molecular mechanisms underlying the GNP efficacy reveals that GNPs downregulate insulin growth factor binding protein 2 (IGFBP2) by disrupting its autoregulation via the IGFBP2/mTOR/PTEN axis. This mechanism is validated by treating a cell line‐based human xenograft tumor with GNPs and an mTOR dual‐kinase inhibitor (PI‐103), either individually or in combination with GNPs; GNP and PI‐103 combination therapy inhibit ovarian tumor growth similarly to GNPs alone. This report illustrates how the self‐therapeutic properties of GNPs can be exploited as a discovery tool to identify a critical signaling axis responsible for poor prognosis in ovarian cancer and provides an opportunity to interrogate the axis to improve patient outcomes.

The heterogeneity of the geographical environment determines the complexity of soil erosion patterns. Determining the effects of changing gradients and combinations of environmental factors on soil erosion is the key to combating soil erosion. In this study, based on the division of the karst development degree, the revised universal soil loss equation model was optimised based on the rocky desertification factor to determine the effect of the different gradients of environmental factors on soil erosion. The geographical detector method was used to identify the dominant and interactive factors of soil erosion under different karst development degrees. The gradient attribution shows that: soil erosion is influenced by the type of bedrock assemblage and the form of the assemblage. Soil erosion is strongest at 1400–1800 m above altitude. Grassland in karst areas is prone to soil erosion and the effect of vegetation coverage on soil erosion has a critical value of 0.6–0.7. Interaction analysis shows that the interaction between land use and slope plays a dominant role in the spatial differentiation of soil erosion, but has significantly higher explanatory power (q)in sub-karst and non-karst areas than in pure-karst areas. Combined with slope and rainfall, soil erosion is obviously intensified, and the pure-karst and sub-karst areas are higher than the non-karst areas. The significant interaction between lithology and slope is a typical feature of karst areas. The findings of this study have crucial theoretical significance for the site-specific control of soil erosion in areas with different karst development degrees.

Post-inflammatory skin hyper- or hypo-pigmentation is a common occurrence with unclear etiology. There is currently no reliable method to predict skin pigmentation outcomes after inflammation. In this study, we analyzed the 5 GEO datasets to screen for inflammatory-related genes involved in melanogenesis, and used candidate cytokines to establish different machine learning (LASSO regression, logistic regression and Random Forest) models to predict the pigmentation outcomes of post-inflammatory skin. Further, to further validate those models, we evaluated the role of these candidate cytokines in pigment cells. We found that IL-37, CXCL13, CXCL1, CXCL2 and IL-19 showed high predictive value in predictive models. All models accurately classified skin samples with different melanogenesis-related gene scores in the training and testing sets (AUC>0.7). Meanwhile, we mainly evaluated the effects of IL-37 in pigment cells, and found that it increased the melanin content and expression of melanogenesis-related genes (MITF, TYR, TYRP1 and DCT), also enhanced tyrosinase activity. In addition, CXCL13, CXCL1, CXCL2 and IL-19 could down-regulate the expression of several melanogenesis-related genes. In conclusion, evaluation models basing on machine learning may be valuable in predicting outcomes of post-inflammatory pigmentation abnormalities. IL-37, CXCL1, CXCL2, CXCL13 and IL-19 are involved in regulating post-inflammatory pigmentation abnormalities.

ObjectiveTo develop an optimal screening model to identify the individuals with a high risk of hypertension in China by comparing tree-based machine learning models, such as classification and regression tree, random forest, adaboost with a decision tree, extreme gradient boosting decision tree, and other machine learning models like an artificial neural network, naive Bayes, and traditional logistic regression models.MethodsA total of 4,287,407 adults participating in the national physical examination were included in the study. Features were selected using the least absolute shrinkage and selection operator regression. The Borderline synthetic minority over-sampling technique was used for data balance. Non-laboratory and semi-laboratory analyses were carried out in combination with the selected features. The tree-based machine learning models, other machine learning models, and traditional logistic regression models were constructed to identify individuals with hypertension, respectively. Top features selected using the best algorithm and the corresponding variable importance score were visualized.ResultsA total of 24 variables were finally included for analyses after the least absolute shrinkage and selection operator regression model. The sample size of hypertensive patients in the training set was expanded from 689,025 to 2,312,160 using the borderline synthetic minority over-sampling technique algorithm. The extreme gradient boosting decision tree algorithm showed the best results (area under the receiver operating characteristic curve of non-laboratory: 0.893 and area under the receiver operating characteristic curve of semi-laboratory: 0.894). This study found that age, systolic blood pressure, waist circumference, diastolic blood pressure, albumin, drinking frequency, electrocardiogram, ethnicity (uyghur, hui, and other), body mass index, sex (female), exercise frequency, diabetes mellitus, and total bilirubin are important factors reflecting hypertension. Besides, some algorithms included in the semi-laboratory analyses showed less improvement in the predictive performance compared to the non-laboratory analyses.ConclusionUsing multiple methods, a more significant prediction model can be built, which discovers risk factors and provides new insights into the prediction and prevention of hypertension.

Although Cisplatin (DDP) is a widely used first-line chemotherapy medication, DDP resistance is one of the main causes of treatment failure in advanced lung cancer. Therefore, it is urgent to identify DDP sensitizers and investigate the underlying molecular mechanisms. Here we utilized DDP-resistant organoids established from tumor biopsies of patients with relapsed lung cancers. In this study, we identified Solamargine as a potential DDP sensitizer through screening a natural product library. Mechanically, Solamargine induced G0/G1-phase arrest and apoptosis in DDP-resistant lung cancer cell lines. Gene expression analysis and KEGG pathway analysis indicated that the hedgehog pathway was suppressed by Solamargine. Moreover, Gli responsive element (GRE) reporter gene assay and BODIPY-cyclopamine binding assay showed that Solamargine inhibited the hedgehog pathway via direct binding to SMO protein. Interestingly, Solamargine and DDP showed a synergetic effect in inhibiting DDP-resistant lung cancer cell lines. Taken together, our work herein revealed Solamargine as a hedgehog pathway inhibitor and DDP-sensitizer, which might provide a new direction for further treatment of advanced DDP-resistant lung cancer patients.

Ferroptosis is a form of non-apoptotic and iron-dependent cell death originally identified in cancer cells. Recently, emerging evidence showed that ferroptosis-targeting therapy could be a novel promising anti-tumour treatment. However, systematic analyses of ferroptosis-related genes for the prognosis of non-small cell lung cancer (NSCLC) and the development of antitumor drugs exploiting the ferroptosis process remain rare. This study aimed to identify genes related to ferroptosis and NSCLC and to initially screen lead compounds that induce ferroptosis in tumor cells. We downloaded mRNA expression profiles and NSCLC clinical data from The Cancer Genome Atlas database to explore the prognostic role of ferroptosis-related genes. Four prognosis-associated ferroptosis-related genes were screened using univariate Cox regression analysis and the lasso Cox regression analysis, which could divide patients with NSCLC into high- and low-risk groups. Then, based on differentially expressed risk- and ferroptosis-related genes, the negatively correlated lead compound flufenamic acid (FFA) was screened through the Connective Map database. This project confirmed that FFA induced ferroptosis in A549 cells and inhibited growth and migration in a dose-dependent manner through CCK-8, scratch, and immunofluorescence assays. In conclusion, targeting ferroptosis might be a therapeutic alternative for NSCLC.

The eutrophication of aquatic ecosystems caused by rapid human urbanization has led to an increased production of potentially hazardous bacterial populations, known as blooms. One of the most notorious forms of these aquatic blooms are cyanobacteria, which in sufficiently large quantities can pose a hazard to human health through ingestion or prolonged exposure. Currently, one of the greatest difficulties in regulating and monitoring these potential hazards is the early detection of cyanobacterial blooms, in real time. Therefore, this paper presents an integrated microflow cytometry platform for label-free phycocyanin fluorescence detection, which can be used for the rapid quantification of low-level cyanobacteria and provide early warning alerts for potential harmful cyanobacterial blooms. An automated cyanobacterial concentration and recovery system (ACCRS) was developed and optimized to reduce the assay volume, from 1000 mL to 1 mL, to act as a pre-concentrator and subsequently enhance the detection limit. The microflow cytometry platform utilizes an on-chip laser-facilitated detection to measure the in vivo fluorescence emitted from each individual cyanobacterial cell, as opposed to measuring overall fluorescence of the whole sample, potentially decreasing the detection limit. By applying transit time and amplitude thresholds, the proposed cyanobacteria detection method was verified by the traditional cell counting technique using a hemocytometer with an R2 value of 0.993. It was shown that the limit of quantification of this microflow cytometry platform can be as low as 5 cells/mL for Microcystis aeruginosa, 400-fold lower than the Alert Level 1 (2000 cells/mL) set by the World Health Organization (WHO). Furthermore, the decreased detection limit may facilitate the future characterization of cyanobacterial bloom formation to better provide authorities with ample time to take the appropriate actions to mitigate human risk from these potentially hazardous blooms.

It is of great practical significance to study the development process of cut lily for regulating flowering and preservation. In this study, the developmental process of lily cut flower was explored from cellular, morphological, and physiological aspects. From a morphological aspect, the tepal edge grows faster than the midrib. The midrib groove of the flowering stage is wider than that of bud stage. The fast-growing edge of the petals results in the midrib bending outward. Moreover, the rapid growth of the stamens and stigmas also contributes to bud cracking. From the cellular aspect, in the bud stage there were more wrinkles in the outer epidermal cell wall of the tepal than those in the inner epidermal cell wall, indicating that asymmetric structural differences exist from the beginning of lily development. From a physiological aspect, from the bud cracking stage to the senescence stage, a variety of substances in the tepal cells gradually decreased, including total nitrogen, total phosphorus, total potassium, total calcium, starch, soluble sugar, and soluble protein, but not malondialdehyde. These results indicate that the asymmetric growth caused by this structural difference is responsible for flowering. The wrinkles in the cell wall can be regarded as indicators of senescent cells and are caused by the degradation of the cell wall and the loss of intracellular turgor pressure. The differences in the epidermal cells between the inner and outer tepal indicated ultrastructural changes in the tepal cells. The bud and flowering stages are maintained by the tepals acting as a sink. After flowering, the tepals gradually change from a sink to a source organ. Senescence of the cut lily flowers was caused by the decomposition of intracellular compounds in the tepals and the remobilization of nutrients from the tepals to the developing organs.

Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment (TME) and an important contributor to cancer progression and therapeutic resistance. Regulation of CAF activation is a promising strategy to influence cancer outcomes. Here, we report that ovarian cancer cells (OCs) and TME cells promote the activation of ovarian CAFs, whereas gold nanoparticles (GNPs) of 20 nm in diameter inhibit the activation, as demonstrated by the changes in cell morphology, migration, and molecular markers. GNPs exert the effect by altering the levels of multiple fibroblast activation or inactivation proteins, such as TGF-β1, PDGF, uPA and TSP1, secreted by OCs and TME cells. Thus, GNPs represent a potential tool to help understand multicellular communications existing in the TME as well as devise strategies to disrupt the communication.

Non-alcoholic fatty liver disease (NAFLD) is a common serious health problem worldwide, which lacks efficient medical treatment. We aimed to develop and validate the machine learning (ML) models which could be used to the accurate screening of large number of people. This paper included 304,145 adults who have joined in the national physical examination and used their questionnaire and physical measurement parameters as model's candidate covariates. Absolute shrinkage and selection operator (LASSO) was used to feature selection from candidate covariates, then four ML algorithms were used to build the screening model for NAFLD, used a classifier with the best performance to output the importance score of the covariate in NAFLD. Among the four ML algorithms, XGBoost owned the best performance (accuracy = 0.880, precision = 0.801, recall = 0.894, F-1 = 0.882, and AUC = 0.951), and the importance ranking of covariates is accordingly BMI, age, waist circumference, gender, type 2 diabetes, gallbladder disease, smoking, hypertension, dietary status, physical activity, oil-loving and salt-loving. ML classifiers could help medical agencies achieve the early identification and classification of NAFLD, which is particularly useful for areas with poor economy, and the covariates' importance degree will be helpful to the prevention and treatment of NAFLD.