Combining (CH2O)n and (NH4)2CO3 as a Formamidine Equivalent for "Four-in-One" Synthesis of Fluoroalkylated 2-H-Pyrimidines.

Multicomponent reactions hold the potential to maximize the synthetic efficiency in the preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for the one-step synthesis of fluoroalkylated 2-H-pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, and ammonium carbonate is described. By harnessing readily accessible (CH2O)n and cheap (NH4)2CO3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with a pyrimidine assembly. The multicomponent reaction proceeds in a step-economical, operationally simple, metal-free, and additive-free manner, featuring a broad substrate scope, excellent functional group compatibility, and scalability. The potential for the synthetic elaboration of the obtained 2-H-pyrimidine is further demonstrated in the alkylation and vinylation of its C2 position.

Robust detection of a rotational Doppler shift with randomly fluctuated light.

The complex external environment, such as obstruction and turbulence, poses significant limitations on the applications of rotational Doppler detection. The active manipulation of randomly fluctuated light has been proven effective in mitigating external environmental perturbations. Here, as an example, a partially coherent source with petal-like focal (or far) field distribution is constructed specifically for detecting rotational Doppler frequency shifts. The experiment involved conducting rotational Doppler detection under obstruction or turbulence conditions, and the results are compared with the fully coherent counterpart. The results demonstrate that the use of a partially coherent source can address the frequency-shift broadening problem due to the obstruction-induced beam information loss and mitigate it due to the turbulence-induced beam misalignment. These advantages make the proposed approach applicable to velocity metrology in complex environments.

The New Pattern for Dual NOTCH Pathway involving Nuclear Transcription and Mitochondrial Regulation Supports Therapeutic Mechanism of 4-butyl benzophenone Derivatives against SIRS.

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFß, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1ß). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway.

Multi-Adaptive Strategies-Based Higher-Order Quantum Genetic Algorithm for Agile Remote Sensing Satellite Scheduling Problem.

The agile remote sensing satellite scheduling problem (ARSSSP) for large-scale tasks needs to simultaneously address the difficulties of complex constraints and a huge solution space. Taking inspiration from the quantum genetic algorithm (QGA), a multi-adaptive strategies-based higher-order quantum genetic algorithm (MAS-HOQGA) is proposed for solving the agile remote sensing satellites scheduling problem in this paper. In order to adapt to the requirements of engineering applications, this study combines the total task number and the total task priority as the optimization goal of the scheduling scheme. Firstly, we comprehensively considered the time-dependent characteristics of agile remote sensing satellites, attitude maneuverability, energy balance, and data storage constraints and established a satellite scheduling model that integrates multiple constraints. Then, quantum register operators, adaptive evolution operations, and adaptive mutation transfer operations were introduced to ensure global optimization while reducing time consumption. Finally, this paper demonstrated, through computational experiments, that the MAS-HOQGA exhibits high computational efficiency and excellent global optimization ability in the scheduling process of agile remote sensing satellites for large-scale tasks, while effectively avoiding the problem that the traditional QGA has, namely low solution efficiency and the tendency to easily fall into local optima. This method can be considered for application to the engineering practice of agile remote sensing satellite scheduling for large-scale tasks.

Effects of the recovery period after particulate matter pollution events on the dust retention capacity and physiological characteristics of Nerium oleander.

Plants are known for their significant dust retention capacity and are widely used to alleviate atmospheric pollution. Urban green plants are exposed to periodic particulate matter pollution stress, and the time intervals between periods of pollution exposure are often inconsistent. The impact of stress memory and pollution intervals on plant dust retention capacity and physiological characteristics during periodic stress is not yet clear. In this study, the common urban landscaping species Nerium oleander L. was selected as the test plant, and stable isotope (15NH4Cl) tracing technology and aerosol generators were used to simulate periodic PM2.5 pollution. This study included two particulate pollution periods (each lasting 14 days) and one recovery period with three different durations (7, 14, and 21 days). The results indicated that periodic particulate matter pollution-induced stress decreased the dust retention capacity of N. oleander leaf surfaces, but particle adsorption to the wax layer was more stable. As the duration of the recovery period increased, leaf particle absorption, which accounted for the greatest proportion of total dust retention, increased, indicating that leaves are the primary organ for dust retention in Nerium oleander L. Root absorption also increased with increasing recovery periods. Prior pollution stress increased oleander physiological and morphological responses, and the plant's air pollution tolerance significantly improved after a recovery period of >14 days.

Silver-Promoted Three-Component Synthesis of Perfluoroalkenyl Pyrroles through Partial Defluorinative Functionalization of Perfluoroalkyl Halides.

A silver-promoted three-component heterocyclization of alkynes, perfluoroalkyl halides, and 1,3-dinucleophiles was developed for the efficient synthesis of privileged (E)-perfluoroalkenyl pyrroles. The reaction proceeded through a rationally designed sequence of radical perfluoroalkylation and intramolecular defluorinative [3 + 2]-heterocyclization. The utility of perfluoroalkyl halide as a perfluoroalkenyl reagent, by selective and controllable functionalization of two inert C(sp3)-F bonds at vicinal carbon centers on the perfluoroalkyl chain, provides a new reaction mode for the synthesis of value-added organofluorides starting from the easily available and low-cost fluorinated feedstock.

Comparing the safety and effectiveness of minimally invasive surgery and open inguinal lymph node dissection in penile cancer: A systematic review and meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of minimally invasive surgery (MIS) with open inguinal lymph node dissection (O-ILND) in penile cancer. METHODS: We performed a systematic reviews and cumulative meta-analyses of primary results of interest according to PRISMA criteria, and quality assessment followed AMSTAR. The system searched five databases, including Zhiwang, Embase, PubMed, Cochrane Library and Web of Science. The search period ranged was from database creation until September 2023. The statistical analysis software used Stata16. RESULTS: A total of 16 studies, including 898 patients. Compared to O-ILND, MIS is superior in length of stay (WMD = -2.96, 95%CI [-4.38, -1.54], P < 0.05), drainage time (WMD = -3.24, 95%CI [-4.70, -1.78], P < 0.05) and estimated blood loss (WMD = -35.70, 95%CI [-46.27, -25.14], P < 0.05), while operation time, recurrence rate and 5-year overall survival rate are the same. The number of lymph nodes dissection between the two groups are not statistically significant. Subgroup analyses found that there are more lymph nodes dissection in robotic-assisted inguinal lymph nodes dissection (WMD = 0.50, 95%CI [0.20, 0.80], P < 0.05). The overall complication rate of MIS was lower (OR = 0.26, 95%CI [0.09, 0.70], P < 0.05). CONCLUSION: Minimally invasive inguinal lymph nodes dissection appears to be a better option for penile cancer cases. But more large samples and multicenter studies are needed to further confirm.

Structural characteristics of cell wall pectic polysaccharides from wampee and their decreased binding with pectinase by wampee polyphenol.

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 105 Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC50 = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables.

[Research Progress of Functional Materials for Conversion of Agricultural Biomass Wastes].

Excess agricultural biomass waste is increasing rapidly, leading to many environmental and governance issues. Therefore, increased attention has been paid to the recycling and value-added application of agricultural biomass waste. In recent years, the research of agricultural biomass waste utilization and derived functional materials has mainly included the following two aspects： ① the extraction of natural polymers and value-added applications and ② the direct preparation of new carbon-based materials, including adsorption, catalysis, energy storage electrode, and composite functional materials. The conversion of agricultural biomass waste into functional materials has been gradually realized and widely used. To enable industrial-scale production and the quality and safety of agricultural biomass waste derivatives and to develop highly feasible and cost-effective biomass waste conversion methods should be the focus of future studies.

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3.

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC). AIM: To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC. METHODS: Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group. RESULTS: Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05). CONCLUSION: Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Photodynamic therapy (PDT) is a promising therapeutic method for managing cSCC due to its proven ability to target specific areas over time and its low risk of side effects. PDT may cause tissue damage and vascular shutdown, and may regulate local immunological responses. The present study aimed to investigate and compare the early lymphocyte modifications before and after PDT for SCC. A total of 10 patients with SCC were identified by pathological investigation. Initially, all wounds were treated with 20% aminolevulinic acid (ALA)-PDT as the initial stage in the therapeutic procedure. The wounds were treated by exposing them to red LED light with a wavelength of 635 nm, an energy density of 100 J/cm2 and an intensity of 80 mW/cm2. The tumor tissue was surgically removed 24 h later, and another round of PDT therapy was administered. Immunohistochemistry for CD3 and CD56 was conducted on the wound tissue post-surgery. If the wound showed granulation, necrosis or secretion, debridement was added to the therapy. All patients were monitored for 0.6-1.0 year post-treatment. ALA-PDT combination surgery fully controlled the tumor tissue in all 10 patients. The immunohistochemical analysis of the wound tissues showed that the expression of CD56 increased, while the expression of CD3 was not different after photodynamic therapy. These results also indirectly indicated that the overall count of NK cells in the 10 patients increased, nevertheless, there was no alteration in the T lymphocyte count. In conclusion, the ALA-PDT combination surgical therapy for cSCC demonstrates favorable results. An increase in CD56 expression may be a mechanism for the effective treatment of cSCC with PDT.

MicroRNA-based interventions in aberrant cell cycle diseases: Therapeutic strategies for cancers, central nervous system disorders and comorbidities.

Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as "aberrant cell cycle re-entry," which plays a critical role in the progression of these diseases. Addressing the dysregulation in cell cycles offers a promising therapeutic approach for cancers and CNS disorders. MicroRNAs (miRNAs) play a crucial role as regulators of gene expression in cell cycle transitions, presenting a promising therapeutic avenue for treating these disorders and their comorbidities. This review consolidates the progress made in the last three years regarding miRNA-based treatments for diseases associated with aberrant cell cycle re-entry. It encompasses exploring fundamental mechanisms and signaling pathways influenced by miRNAs in cancers and CNS disorders, particularly focusing on the therapeutic effects of exosome-derived miRNAs. The review also identifies specific miRNAs implicated in comorbidity of cancers and CNS disorders, discusses the future potential of miRNA reagents in managing cell cycle-related diseases.

Impact of urban space on PM2.5 distribution: A multiscale and seasonal study in the Yangtze River Delta urban agglomeration.

Despite concerted efforts in emission control, air pollution control remains challenging. Urban planning has emerged as a crucial strategy for mitigating PM2.5 pollution. What remains unclear is the impact of urban form and their interactions with seasonal changes. In this study, base on the air quality monitoring stations in the Yangtze River Delta urban agglomeration, the relationship between urban spatial indicators (building morphology and land use) and PM2.5 concentrations was investigated using full subset regression and variance partitioning analysis, and seasonal differences were further analysed. Our findings reveal that PM2.5 pollution exhibits different sensitivities to spatial scales, with higher sensitivity to the local microclimate formed by the three-dimensional structure of buildings at the local scale, while land use exerts greater influence at larger scales. Specifically, land use indicators contributed sustantially more to the PM2.5 prediction model as buffer zone expand (from an average of 2.41% at 100 m range to 47.30% at 5000 m range), whereas building morphology indicators display an inverse trend (from an average of 13.84% at 100 m range to 1.88% at 5000 m range). These results enderscore the importance of considering building morphology in local-scale urban planning, where the increasing building height can significantly enhance the disperion of PM2.5 pollution. Conversely, large-scale urban planning should prioritize the mixed use of green spaces and construction lands to mitigate PM2.5 pollution. Moreover, the significant seasonal differences in the ralationship between urban spatical indicatiors and PM2.5 pollution were observed. Particularly moteworthy is the heightened association between forest, water indicators and PM2.5 concentrations in summer, indicating the urban forests may facilitate the formation of volatile compunds, exacerbating the PM2.5 pollution. Our study provides a theoretical basis for addressing scale-related challenges in urban spatial planning, thereby forstering the sustainable development of cities.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge ( P =0.429) and 6 months after surgery ( P =1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus ( P =0.088), D dimer ( P =0.412), catheter in situ days ( P =0.281), and post-thrombotic syndrome ( P =1.000), except for activated partial thromboplastin time ( P =0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.

Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.

Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.

Background: The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function. Materials and methods: Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV1, FVC, and FEV1/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results. Results: The MR results confirmed four taxa were found causally associated with the risk of IPF. Order Bifidobacteriales (OR=0.773, 95% CI: 0.610-0.979, p=0.033), Family Bifidobacteriaceae (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and Genus RuminococcaceaeUCG009 (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while Genus Coprococcus2 (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in Class Deltaproteobacteria, Order Desulfovibrionales, Family Desulfovibrionaceae, Class Verrucomicrobiae, Order Verrucomicrobiales and Family Verrucomicrobiaceae being the most prominent beneficial microbiota, while those in Family Lachnospiraceae, Genus Oscillospira, and Genus Parasutterella were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV1 and FVC on the increased abundance of six taxa (Phylum Actinobacteria, Class Actinobacteria, Order Bifidobacteriales, Family Bifidobacteriaceae, Genus Bifidobacterium, and Genus Ruminiclostridium9) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF. Conclusion: The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.

Correlation of TyG-BMI and TyG-WC with severity and short-term outcome in new-onset acute ischemic stroke.

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.

Progressively worsening ptosis in a woman: A case report.

Key Clinical Message: Filler injections into the upper eyelid may cause levator aponeurosis fibrosis and ptosis. This risk must be considered. When ptosis appears, treatment might be difficult. Understanding the upper eyelid anatomy and procedures is essential to prevent eyelid damage. Abstract: Ptosis is a prevalent condition in cosmetic surgery that occurs due to malfunction of the levator palpebrae superioris or insufficient Müller muscle action. It is characterized by the upper eyelid edge appearing lower than usual when seen at eye level. Ptosis may be categorized into congenital and acquired forms. The primary cause of congenital ptosis is attributed to abnormalities of the levator palpebrae superioris muscle or the motor nerve innervation that controls it. The condition arises from atypical development and malfunction of the oculomotor system. Acquired ptosis may be classified into many categories including traumatic, neurogenic, myogenic, senile, mechanical, and fake ptosis. Currently, there is little documentation of ptosis resulting from the degeneration of the aponeurosis of the muscle in the upper eyelid. We received a case of ptosis caused by fibrosis of the levator palpebrae superioris aponeurotic membrane. We used the technique of levator palpebrae superioris great advancement. The levator palpebrae superioris-Müller muscle was folded to create a stable composite construction via the levator palpebrae superioris high progress.