Search

Abstract The characteristics of fan sediment in the distributive fluvial system are evaluated based on a thorough analysis of modern silt in the Guertu river distributive fluvial system, as well as data obtained from UAV aerial photography and satellite remote sensing. The Guertu River Distributive Fluvial System (DFS) is classified into three stages, namely "proximal," "middle," and "distal," based on the examination of river morphology, sediment variations, sedimentary attributes, and other relevant aspects throughout different sections of its tributaries, from the source to the mouth. At the upstream section of the downstream fining sequence, the slope is the steepest and the hydrodynamic conditions are intense, resulting in the formation of a predominantly big gravel braided river. The river bed section has a morphology resembling a combination of a "V" and a "U" shape. It is characterized by a narrow and deep configuration, with a relatively short breadth. The sediment primarily consists of medium to large-sized gravel with minimal sand content. The gravel exhibits good roundness and displays a considerable degree of orientation. The primary microfacies present are braided channel and flood plain. The slope of the central area is decreased in comparison to the nearby end, primarily due to the presence of extensive braided rivers. The river bed has a greater width, with minor eolian dunes visible in the river channel. The gravel particles are predominantly fine to medium in size, and there is an increased amount of sand present. The predominant microfacies are braided channels, floodplains, and eolian dunes. At the distal end, the slope is minimal, the landscape is level, the braided river transitions into a meandering river, the sediment consists primarily of sand, and the signs of bioturbation are clearly visible. The primary microfacies consist of braided channels, meandering channels, floodplains, eolian dunes, lakes, and swamps.

Abstract Background Case-based learning (CBL) utilizing three-dimensional (3D) printed hip joint models is a problem-solving teaching method that combines the tactile and visual advantages of 3D-printed models with CBL. This study aims to investigate the impact of integrating 3D printing with CBL on learning developmental dysplasia of the hip (DDH). Methods We conducted a prospective study from 2022 to 2023, including 120 fourth-year clinical medical students at Xuzhou Medical University. Students were randomly allocated into two groups of 60 participants each. The CBL group received conventional CBL teaching methods, while the 3D + CBL group utilized 3D-printed models in conjunction with CBL. Post-teaching, we analyzed and compared the theoretical and practical achievements of both groups. A questionnaire was designed to assess the impact of the educational approach on orthopedic surgery learning. Results The theory scores of the CBL group (62.88 ± 7.98) and 3D + CBL group (66.35 ± 8.85) were significantly different (t = 2.254, P = 0.026); the practical skills scores of the CBL group (57.40 ± 8.80) and 3D + CBL group (63.42 ± 11.14) were significantly different (t = 3.283, P = 0.001). The questionnaire results showed that the 3D + CBL group was greater than the CBL group in terms of hip fundamentals, ability to diagnose cases and plan treatments, interesting teaching content, willingness to communicate with the instructor and satisfaction. Conclusions The integration of 3D printing with case-based learning has yielded positive outcomes in teaching DDH, providing valuable insights into the use of 3D-printed orthopedic models in clinical education.

Objective: Hot air coupled with ultrasound and infrared irradiation were used for the drying of curdlan. The drying mechanism and quality change of curdlan were explored under the multi-physical fields, so as to developing the green drying technology of curdlan. Methods: Forced convective hot air alone, ultrasound-coupled forced convective hot air, infrared irradiation alone, and infrared-coupled forced convective hot air were used to dry curdlan. A mass transfer model considering temeprature change was constructed and the quality of the dried curdlan was comprehensively assessed. Results: Under the studied forced convective hot air drying conditions, it took around 40 min to dry the curdlan, and the required drying time was reduced to 36, 26 and 22 min for ultrasound-coupled hot air drying, infrared irradiation alone drying, and infrared-coupled hot air drying, respectively. The moisture transfer model coupled with the temperature change was able to accurately predict the change of the moisture content throughout drying. Under infrared drying coupled with convective hot air, the range of moisture effective diffusivity inside curdlan was 9.79×10−9 to 9.81×10−9 m2/s, and the surface mass transfer coefficient was 4.69×10−2 kg water/(m2·s), which were higher than those of the other treatment groups, followed by those under infrared irradiation alone drying, ultrasonic-coupled hot air drying, and hot air drying alone. Moreover, the gel strength, glucose content, the distribution of chemical functional groups on surface, crystal structure and thermal stability of curdlan samples dried by different methods were all similar. Conclusion: Taking all these results into consideration, infrared drying was regarded as an efficient method for drying curdlan compared to hot air drying and ultrasound-coupled hot air drying.

Phlomoides bomiensis, a new species in Bomi County, Xizang, China, was described and illustrated. In addition, Phlomoides longidentata, previously only known from Nepal and Bhutan, is newly recorded from Dingri County, Xizang, China. The phylogenetic placement of both species within the genus was analysed using nine plastid DNA markers (atpB-rbcL, psbA-trnH, rpl16, rpl32-trnL, rps16, trnK, trnL-trnF, trnS-trnG, trnT-trnL). Both species have brown-black trichomes inside the upper corolla lip and nested within the same subclade of Clade II. A diagnostic key to the Phlomoides species belonging to this subclade is provided.

Abstract Background Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. Methods The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People’s Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. Results The overall HPV infection rate at the First People’s Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20–29 age group and 13.84% in the 30–39 age group, followed by a gradual increase to 14.64% in the 40–49 age group, 16.65% in the 50–59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. Conclusion There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Abstract In the realm of natural supersymmetric models, higgsinos are typically the lightest electroweakinos. In gauge-mediated supersymmetry breaking models, the lightest higgsino-dominated particles decay into a Z-boson or a Higgs boson (h), along with an ultra-light gravitino ( $$\tilde{G}$$ G ~ ) serving as the lightest supersymmetric particle (LSP). This scenario suggests a significant non-resonant hh production. Basing on the recent global fitting results of the $$\tilde{G}$$ G ~ -EWMSSM (MSSM with light electroweakinos and an eV-scale gravitino as the LSP) performed by the GAMBIT collaboration, which support a higgsino-dominated electroweakino as light as 140 GeV, we develop two simplified models to evaluate their detection potential at the high-luminosity LHC (HL-LHC) with $$\sqrt{s} = 14~\textrm{TeV}$$ s = 14 TeV and an integrated luminosity of $$3000~\textrm{fb}^{-1}$$ 3000 fb - 1 . The first model examines the processes where heavier higgsino-dominated states decay into soft W/Z bosons, while the second focuses on direct decays of all three higgsino-dominated electroweakinos into W/Z/h plus a $$\tilde{G}$$ G ~ . Our study, incorporating both models and their distinct decay channels, utilizes detailed Monte Carlo simulations for signals and standard model backgrounds. We find that the HL-LHC can probe higgsinos up to 575 GeV, potentially discovering or excluding the natural SUSY scenario in the context of a gravitino LSP. Further, we reinterpret this discovery potential using the GAMBIT global fit samples, and find that the entire parameter space of $$|\mu | \le 500~\textrm{GeV}$$ | μ | ≤ 500 GeV with an electroweak fine-tuning measure ( $$\Delta _{\textrm{EW}}$$ Δ EW ) under 100 in $$\tilde{G}$$ G ~ -EWMSSM is accessible at the HL-LHC.

Abstract Locally resonant metamaterials usually have narrow bandgaps, which significantly limits their applications in realistic engineering environments. In this paper, an optimization method based on the genetic algorithm is proposed to broaden bandgaps in multi-resonant piezoelectric metamaterial through the merging of multiple separated bandgaps. Using the effective medium theory, the equivalent bending stiffness and dispersion relationship of a metamaterial plate are first obtained. Then, the criteria for determining the bandgap ranges for the two cases with and without damping are provided and analyzed. Furthermore, based on the bandgap merging phenomena, an optimization method for widening the bandgap is proposed based on the genetic algorithm. By investigating the bandgap widening effects in cases without and with damping, it is found that, when there is no damping, the bandgap can only be slightly widened; while after introducing damping into the transfer functions, the bandgap can be significantly widened by more than 200%. The bandgap widening effects are verified by comparing with finite element simulation results.

Abstract Background Tumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical trials. A better understanding of the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia is needed for future clinical application. Here, we investigated the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia in patients with localized PCa, in order to apply PIMO as a prognostic tool and to identify potential biomarkers for future clinical translation. Methods A total of 39 patients with localized PCa were recruited and administered oral PIMO before undergoing radical prostatectomy (RadP). Immunohistochemical staining for PIMO was performed on 37 prostatectomy specimens with staining patterns evaluated and clinical association analyzed. Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative tumor areas. A hypoxia related methylation molecular signature was generated by integrating the differentially methylated regions with previously established RNA-seq datasets. Results Three PIMO staining patterns were distinguished: diffuse, focal, and comedo-like. The comedo-like staining pattern was more commonly associated with adverse pathology. PIMO-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology. The generated DNA methylation signature was found to be a robust hypoxia biomarker, which could risk-stratify PCa patients across multiple clinical datasets, as well as be applicable in other cancer types. Conclusions Oral PIMO unveiled clinicopathologic features of disease aggressiveness in localized PCa. The generated DNA methylation signature is a novel and robust hypoxia biomarker that has the potential for future clinical translation.

Abstract The prognosis for Cutaneous Melanoma (CM), a skin malignant tumor that is extremely aggressive, is not good. A recently identified type of controlled cell death that is intimately related to immunotherapy and the development of cancer is called cuproptosis. Using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we developed and validated a DNA-methylation located in cuproptosis death-related gene prognostic signature (CRG-located DNA-methylation prognostic signature) to predict CM’s prognosis. Kaplan–Meier analysis of our TCGA and GEO cohorts showed that high-risk patients had a shorter overall survival. The area under the curve (AUC) for the TCGA cohort was 0.742, while for the GEO cohort it was 0.733, according to the receiver operating characteristic (ROC) analysis. Furthermore, this signature was discovered as an independent prognostic indicator over CM patients based on Cox-regression analysis. Immunogenomic profiling indicated that majority immune-checkpoints got an opposite relationship with the signature, and patients in the group at low risk got higher immunophenoscore. Several immune pathways were enriched, according to functional enrichment analysis. In conclusion, a prognostic methylation signature for CM patients was established and confirmed. Because of its close relationship to the immune landscape, this signature may help clinicians make more accurate and individualized choices regarding therapy.

Abstract Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02–1.09), vascular dementia (HR, 1.08; 95% CI 1.01–1.15), and non-Alzheimer’s disease non-vascular dementia (HR, 1.09; 95% CI 1.03–1.14). No significant association was observed for Alzheimer’s disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Abstract Objective The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). Methods This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. Results In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p

Abstract Background Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. Results In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. Conclusion Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Abstract Manipulating liquid flow over open solid substrate at nanoscale is important for printing, sensing, and energy devices. The predominant methods of liquid maneuvering usually involve complicated surface fabrications, while recent attempts employing external stimuli face difficulties in attaining nanoscale flow control. Here we report a largely unexplored ion beam induced film wetting (IBFW) technology for open surface nanofluidics. Local electrostatic forces, which are generated by the unique charging effect of Helium focused ion beam (HFIB), induce precursor film of ionic liquid and the disjoining pressure propels and stabilizes the nanofilm with desired patterns. The IBFW technique eliminates the complicated surface fabrication procedures to achieve nanoscale flow in a controllable and rewritable manner. By combining with electrochemical deposition, various solid materials with desired patterns can be produced.

Background Neoadjuvant chemoimmunotherapy has a promising effect on locally advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers robustly predicting therapeutic response are still lacking.Methods Formalin-fixed and paraffin-embedded pre-neoadjuvant chemoimmunotherapy biopsy samples from locally advanced ESCC patients were collected. Cohort 1 composed of 66 locally advanced ESCC patients from a prospective clinical trial (NCT04506138) received two cycles of camrelizumab in combination with nab-paclitaxel and carboplatin every 3 weeks. Cohort 2 included 48 patients receiving various types of immune checkpoint inhibitors with (nab-)paclitaxel and platinum-based chemotherapy as neoadjuvant therapy. Cohort 3 consisted of 27 ESCC patients receiving neoadjuvant treatment of toripalimab with chemotherapy and was used as the external validation dataset. Targeted RNA sequencing, immunohistochemistry for programmed death ligand 1 (PD-L1), and multiplex immunofluorescence (mIF) imaging were performed.Results Integration of targeted RNA sequencing, PD-L1 immunohistochemistry, and mIF revealed a significant immune-suppressive microenvironment with higher neutrophil infiltration, enriched TGF-β, and cell cycle pathways in non-pathological complete response (non-pCR) patients. NK, activated CD4+ T cell infiltration, interferon-gamma, antigen processing and presentation, and other immune response signatures were significantly associated with pCR. Based on discovered tumor microenvironmental characteristics and their closely related genes were screened. Consequently, a seven-gene neoadjuvant chemoimmunotherapy risk prediction signature (NCIRPs) model, was constructed. In addition to cohort 1, this model alone or with PD-L1-combined positive score (CPS) demonstrated a higher prediction accuracy of pathological response than PD-L1 CPS or other routinely used immune signatures, such as IFN-γ, in cohorts 2 and 3. Neither prognostic association nor correlation with response to chemoradiotherapy was observed in The Cancer Genome Atlas Program ESCC dataset or in ESCC patients in the neoadjuvant chemoradiotherapy cohort (cohort 4).Conclusion The NCIRPs model that was developed and validated using treatment-naïve endoscopic samples from the largest ESCC neoadjuvant chemoimmunotherapy dataset represents a robust and clinically meaningful approach to select a putative responder for neoadjuvant chemoimmunotherapy in locally advanced ESCC patients.

Renal calyceal neck atresia is a rare disorder. There is no clear guidance for standard treatment of this condition. The Memokath™ 045 temperature-controlled memory alloy stent is commonly used in the treatment of urethral strictures, but it has not been used for treating calyceal neck atresia. We present a case of a 44-year-old female patient with left lumbar pain who underwent two stages of treatment to resolve calyceal neck atresia located at the upper calyx of her left kidney. The first procedure was transurethral ureteroscopy combined with percutaneous recanalization of the left upper calyx calyceal neck atresia. One 6 F internal stent and one 8 F internal stent were placed, and she was discharged with a left nephrostomy tube. After her urinary tract infection was fully resolved, the patient returned for the second procedure of percutaneous upper renal calyx calyceal neck metal stent implantation. The temporary stents and nephrostomy tube were successfully removed. Our findings suggest that the Memokath™ 045 temperature-controlled memory alloy stent is an effective choice for treating calyceal neck atresia.

BackgroundsUlcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC.MethodsWe reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC.ResultsThe results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III.ConclusionThis review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.

BackgroundPeople who undergo sphincter-preserving surgery have high rates of anorectal functional disturbances, known as low anterior resection syndrome (LARS). LARS negatively affects patients’ quality of life (QoL) and increases their need for self-management behaviors. Therefore, approaches to enhance self-management behavior and QoL are vital. ObjectiveThis study aims to assess the effectiveness of a remote digital management intervention designed to enhance the QoL and self-management behavior of patients with LARS. MethodsFrom July 2022 to May 2023, we conducted a single-blinded randomized controlled trial and recruited 120 patients with LARS in a tertiary hospital in Hefei, China. All patients were randomly assigned to the intervention group (using the “e-bowel safety” applet and monthly motivational interviewing) or the control group (usual care and an information booklet). Our team provided a 3-month intervention and followed up with all patients for an additional 3 months. The primary outcome was patient QoL measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. The secondary outcomes were evaluated using the Bowel Symptoms Self-Management Behaviors Questionnaire, LARS score, and Perceived Social Support Scale. Data collection occurred at study enrollment, the end of the 3-month intervention, and the 3-month follow-up. Generalized estimating equations were used to analyze changes in all outcome variables. ResultsIn the end, 111 patients completed the study. In the intervention group, 5 patients withdrew; 4 patients withdrew in the control group. Patients in the intervention group had significantly larger improvements in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 total score (mean difference 11.51; 95% CI 10.68-12.35; Cohen d=1.73) and Bowel Symptoms Self-Management Behaviors Questionnaire total score (mean difference 8.80; 95% CI 8.28-9.32; Cohen d=1.94) than those in the control group. This improvement effect remained stable at 3-month follow-up (mean difference 14.47; 95% CI 13.65-15.30; Cohen d=1.58 and mean difference 8.85; 95% CI 8.25-9.42; Cohen d=2.23). The LARS score total score had significantly larger decreases after intervention (mean difference –3.28; 95% CI –4.03 to –2.54; Cohen d=–0.39) and at 3-month follow-up (mean difference –6.69; 95% CI –7.45 to –5.93; Cohen d=–0.69). The Perceived Social Support Scale total score had significantly larger improvements after intervention (mean difference 0.47; 95% CI 0.22-0.71; Cohen d=1.81). ConclusionsOur preliminary findings suggest that the mobile health–based remote interaction management intervention significantly enhanced the self-management behaviors and QoL of patients with LARS, and the effect was sustained. Mobile health–based remote interventions become an effective method to improve health outcomes for many patients with LARS. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200061317; https://tinyurl.com/tmmvpq3

Silty soil was widely used as filling soil materials for the replacement of expansive soil in cold regions. This paper presents a straightforward approach for the effects of wetting-drying-freezing-thawing cycles on mechanical behaviors of silty soil and expansive soil by laboratory tests. The results showed that the silty soil and expansive soil after 7th wetting-drying-freezing-thawing cycles presented the decreases of elastic modulus, failure strength, cohesion and angel of internal friction by 8.9 %∼12.0 %, 7.7 %∼9.0 %, 7.9 %, 4.5 % and 17.6 %∼37.0 %, 20.5 %∼29.4 %, 43.2 %, 13.0 %, respectively, indicating that wetting-drying-freezing-thawing cycles had little impact on mechanical property of silty soil and a great influence on that of expansive soil. Among them, the mechanical property attenuation ratio in the first three wetting-drying-freezing-thawing cycles accounted for over 90 % of the total. In the meantime, the micro-structure damage, surface crack characteristics and grain size distribution variations of expansive soil were all more significantly than these of silty soil exposed to wetting-drying-freezing-thawing cycles, which brought insight into the causes of the differences in mechanical properties for silty soil and expansive soil. It is found that the silty soil properties were more stable than expansive soil properties, and the silty soil is very effective for replacing the expansive soil below canal structures in cold regions.

PurposeTo elucidate the reasons behind the increased incidence of ocular disease in patients with coronavirus disease 2019 (COVID-19), this study delved deeper into the specific effects of COVID-19 on patients’ ocular surface microbiome (OSM) and investigated its relationship with the increased incidence of ocular disease.MethodsIn this study, conjunctival sac swabs were collected from 43 participants for 16S rRNA amplicon sequencing. The participants were categorized into three groups based on their COVID-19 status: the control group (C group) consisted of 15 participants who showed no evidence of COVID-19, the experimental group (E group) included 15 participants who tested positive for COVID-19, and the COVID-19 recovery period group (R group) comprised 13 participants.ResultsIn the comparison of alpha diversity, group E had a higher Shannon, Chao1 and Goods coverage index. When comparing beta diversity, groups E and R were more similar to each other. At the phylum level, although the OSM of the three groups was dominated by Proteobacteria, Actinobacteriota, Bacteroidota and Firmicutes, the compositional proportions were significantly different. At the genus level, the dominant species in the three OSM groups were significantly different, with Pseudomonas becoming the dominant genus in groups E and R compared to group C, and the abundance of Ralstonia decreasing significantly.ConclusionThis study provides additional evidence supporting the association between the OSM and COVID-19, which contributes to our understanding of the potential mechanisms underlying ocular symptoms and complications associated with COVID-19 in the future.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

BackgroundPathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk.MethodsIn this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites.ResultsThis study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27–2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30–4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003–1.048, P=0.026).ConclusionGenetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.

Summary: In this study, the theoretical calculations proves that the combination of oxygen vacancy and amorphous carbon films in TiO2 (VO-CT) can effectively reduce the energy bandgap and work function. The minimum Gibbs free energies required for the CO2RR reaction of VO-CT are 0.20 eV, which is lower than pure TiO2. The amorphous c@TiO2 nanomaterials with oxygen vacancy and mesoporous structures (VO-MCT) are prepared with the P123 surfactant as the template and oxalic acid as an inducer. The electron paramagnetic resonance indicates the presence of abundant oxygen vacancy defects in the samples. UV-vis spectra indicate that the mesoporous structure enhances light absorption capacity. The photocatalytic CO2 reduction tests show that the highest conversion rates for CH4 and CO of VO-MCT are 14 μmol g−1 h−1 and 10.66 μmol g−1 h−1, respectively. The electron consumption rate of VO-MCT is 12.43 times higher than that of commercial TiO2 (P200).

Existing Land Surface Temperature (LST) fusion models encounter some challenges due to missing data, complex weather areas, and rapid land cover changes. To overcome these limitations, we proposed the Integrated SpatioTemporal Fusion Algorithm (ISFAT). ISFAT is developed based on contemporary fusion models but in addition incorporates data from partially contaminated LSTs using the masked weight function. This helps to predict fine-scale LST on prediction date while considering error resulting from landcover changes between the base and prediction date. This algorithm also factors in the calculation of model residuals, which are distributed back to the predicted fine-scale LST using the thin-plate spline function. The fine-scale LST on prediction can thereafter employed for predicting hourly fine-scale LST images by integrating a coarse resolution LST with hourly temporal resolution. Compared to contemporary LST fusion models, ISFAT demonstrates superior performance, with mean average differences of 0.1 K and 0.27 K over SADFAT and STITFM, respectively. Additionally, diurnal LST predictions from ISFAT compare well with air temperatures from automatic weather stations. Notably, on February 18, 2020, ISFAT effectively optimized fine-scale LST for Hong Kong, achieving an RMSE of 3.33 K, despite the limitation of cloud cover in the base date. The newly developed ISFAT could facilitate better LST retrieval over a large spatial coverage under different degrees of cloud contamination.

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic drug model, has received widespread attention from academia and the pharmaceutical industry. PROTAC technology has led researchers to focus on developing chemical biology tool properties due to the unique operating mechanism and protein dynamic regulatory properties. In recent years the rapid development of PROTAC technology has gradually made PROTACs an essential tool for target identification and validation. To further promote the application of PROTAC tools in drug discovery and basic medical science research, this review distinguished target identification and validation concepts. Furthermore, research progress in PROTAC technology was summarized.

Objective To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. Methods High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. Results The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. Conclusion ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Abstract Background Astragaloside IV (As-IV) and Tanshinone IIA (Ta-IIA) are the main ingredients of traditional Chinese medicinal Astragalus membranaceus (Fisch.) Bunge and Salvia miltiorrhiza Bunge, respectively, both of which have been employed in the treatment of cardiovascular diseases. Nevertheless, the efficacy of the combination (Co) of Ta-IIA and As-IV for cardiovascular diseases remain unclear and warrant further investigation. This study aimed to investigate the efficacy and the underlying molecular mechanism of Co in treating myocardial ischemia–reperfusion injury (MIRI). Methods In order to assess the efficacy of Co, an in vivo MIRI mouse model was created by temporarily blocking the coronary arteries for 30 min and then releasing the blockage. Parameters such as blood myocardial enzymes, infarct size, and ventricular function were measured. Additionally, in vitro experiments were conducted using HL1 cells in both hypoxia-reoxygenation model and oxidative stress models. The apoptosis rate, expression levels of apoptosis-related proteins, oxidative stress indexes, and release of inflammatory factors were detected. Furthermore, molecular docking was applied to examine the binding properties of Ta-IIA and As-IV to STING, and western blotting was performed to analyze protein expression of the STING pathway. Additionally, the protective effect of Ta-IIA, As-IV and Co via inhibiting STING was further confirmed in models of knockdown STING by siRNA and adding STING agonist. Results Both in vitro and in vivo data demonstrated that, compared to Ta-IIA or As-IV alone, the Co exhibited superior efficacy in reducing the area of myocardial infarction, lowering myocardial enzyme levels, and promoting the recovery of myocardial contractility. Furthermore, the Co showed more potent anti-apoptosis, antioxidant, and anti-inflammation effects. Additionally, the Co enhanced the inhibitory effects of Ta-IIA and As-IV on STING phosphorylation and the activation of STING signaling pathway. However, the administration of a STING agonist attenuated the protective effects of the Co, Ta-IIA, and As-IV by compromising their anti-apoptotic, antioxidant, and anti-inflammatory effects in MIRI. Conclusion Compared to the individual administration of Ta-IIA or As-IV, the combined treatment demonstrated more potent ability in inhibiting apoptosis, oxidative stress, inflammation, and the STING signaling pathway in the context of MIRI, indicating a more powerful protective effect against MIRI. Graphical Abstract

In order to improve the energy output consistency of 3, 3′-diamino-4, 4′-azoxyfurazan (DAAF) in the new insensitive booster and the safety and efficiency in the preparation process, a continuous preparation system of DAAF from synthesis to spherical coating was designed and established in this paper, which combined ultrasonic micromixing reaction with microdroplet globular template. In the rapid micromixing stage, the microfluidic mixing technology with ultrasonic was used to synergistically strengthen the uniform and rapid mass transfer mixing reaction between raw materials to ensure the uniformity of DAAF particle nucleation-growth, and to prepare high-quality DAAF crystals with uniform structure and morphology and concentrated particle size distribution. In the microdroplet globular template stage, the microfluidic droplet technology was used to form a droplet globular template with uniform size under the shear action of the continuous phase of the dispersed phase solution containing DAAF particles and binder. The size of the droplet template was controlled by adjusting the flow rate ratio between the continuous phase and the dispersed phase. In the droplet globular template, with the diffusion of the solvent in the dispersed phase droplets, the binder precipitates to coat the DAAF into a ball, forming a DAAF microsphere with high sphericity, narrow particle size distribution and good monodispersity. The problem of discontinuity and DAAF particle suspension in the process was solved, and the coating theory under this process was studied. DAAF was coated with different binder formulations of fluororubber (F2604), nitrocellulose (NC) and NC/glycidyl azide polymer (GAP), and the process verification and evaluation of the system were carried out. The balling effects of large, medium and small droplet templates under different binder formulations were studied. The scanning electron microscope (SEM) results show that the three droplet templates under the three binder formulations exhibit good balling effect and narrow particle size distribution. The DAAF microspheres were characterized by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermo-gravimetric (TG) and sensitivity analyzer. The results showed that the crystal structure of DAAF did not change during the process, and the prepared DAAF microspheres had lower decomposition temperature and lower mechanical sensitivity than raw DAAF. The results of detonation parameters show that the coating of DAAF by using the above three binder formulations will not greatly reduce the energy output of DAAF, and has comparable detonation performance to raw DAAF. This study proves an efficient and safe continuous system from synthesis to spherical coating modification of explosives, which provides a new way for the continuous, safe and efficient preparation of spherical explosives.

Abstract Non-orthogonal eigenstates are a fundamental feature of non-Hermitian systems and are accompanied by the emergence of nontrivial features. However, the platforms to explore non-Hermitian mode couplings mainly measure near-field effects, and the far-field behaviours remain mostly unexplored. Here, we study how a microcavity with non-Hermitian mode coupling exhibits eigenstate non-orthogonality by investigating the spatial field and the far-field polarization of cavity modes. The non-Hermiticity arises from asymmetric backscattering, which is controlled by integrating two scatterers of different size and location into a microdisk. We observe that the spatial field overlap of two modes increases abruptly to its maximum value, whilst different far-field elliptical polarizations of two modes coalesce when approaching an exceptional point. We demonstrate such features experimentally by measuring the far-field polarization from the fabricated microdisks. Our work reveals the non-orthogonality in the far-field degree of freedom, and the integrability of the microdisks paves a way to integrate more non-Hermitian optical properties into nanophotonic systems.