Identification and analysis of prognostic immune cell homeostasis characteristics in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most invasive malignant tumor of the respiratory system. It is also the common pathological type leading to the death of LUAD. Maintaining the homeostasis of immune cells is an important way for anti-tumor immunotherapy. However, the biological significance of maintaining immune homeostasis and immune therapeutic effect has not been well studied. METHODS: We constructed a diagnostic and prognostic model for LUAD based on B and T cells homeostasis-related genes. Minimum absolute contraction and selection operator (LASSO) analysis and multivariate Cox regression are used to identify the prognostic gene signatures. Based on the overall survival time and survival status of LUAD patients, a 10-gene prognostic model composed of ABL1, BAK1, IKBKB, PPP2R3C, CCNB2, CORO1A, FADD, P2RX7, TNFSF14, and ZC3H8 was subsequently identified as prognostic markers from The Cancer Genome Atlas (TCGA)-LUAD to develop a prognostic signature. This study constructed a gene prognosis model based on gene expression profiles and corresponding survival information through survival analysis, as well as 1-year, 3-year, and 5-year ROC curve analysis. Enrichment analysis attempted to reveal the potential mechanism of action and molecular pathway of prognostic genes. The CIBERSORT algorithm calculated the infiltration degree of 22 immune cells in each sample and compared the difference of immune cell infiltration between high-risk group and low-risk group. At the cellular level, PCR and CKK8 experiments were used to verify the differences in the expression of the constructed 10-gene model and its effects on cell viability, respectively. The experimental results supported the significant biological significance and potential application value of the molecular model in the prognosis of lung cancer. Enrichment analyses showed that these genes were mainly related to lymphocyte homeostasis. CONCLUSION: We identified a novel immune cell homeostasis prognostic signature. Targeting these immune cell homeostasis prognostic genes may be an alternative for LUAD treatment. The reliability of the prediction model was confirmed at bioinformatics level, cellular level, and gene level.

ADCY4 promotes brain metastasis in small cell lung cancer and is associated with energy metabolism.

Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI-H209 and NCI-H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.

Multi-Scale Analysis of the Damage Evolution of Coal Gangue Coarse Aggregate Concrete after Freeze-Thaw Cycle Based on CT Technology.

This study utilized X-ray computed tomography (CT) technology to analyze the meso-structure of concrete at different replacement rates, using a coal gangue coarse aggregate, after experiencing various freeze-thaw cycles (F-Ts). A predictive model for the degradation of the elastic modulus of Coal Gangue coarse aggregate Concrete (CGC), based on mesoscopic damage, was established to provide an interpretation of the macroscopic mechanical behavior of CGC after F-Ts damage at a mesoscopic scale. It was found that after F-Ts, the compressive strength of concrete, with coal gangue replacement rates of 30%, 60%, and 100%, respectively, decreased by 33.76%, 34.89%, and 42.05% compared with unfrozen specimens. The results indicate that an increase in the coal gangue replacement rate exacerbates the degradation of concrete performance during the F-Ts process. Furthermore, the established predictive formula for elastic modulus degradation closely matches the experimental data, offering a reliable theoretical basis for the durability design of CGC in F-Ts environments.

Multiplexed Short-wave Infrared Imaging Highlights Anatomical Structures in Mice.

While multiplexed fluorescence imaging is frequently used for in vitro microscopy, extending the technique to whole animal imaging in vivo has remained challenging due to the attenuation and scattering of visible and traditional near infrared (NIR-I) wavelengths. Fluorescence imaging using short-wave infrared (SWIR, 1000 - 1700 nm, a.k.a. NIR-II) light enables deeper tissue penetration for preclinical imaging compared to previous methods due to reduced tissue scattering and minimal background autofluorescence in this optical window. Combining NIR-I excitation wavelengths with multiple distinct SWIR emission peaks presents a tremendous opportunity to distinguish multiple fluorophores with high precision for non-invasive, multiplexed anatomical imaging in small animal models. SWIR-emitting semiconductor quantum dots (QDs) with tunable emission peaks and optical stability have emerged as powerful contrast agents, but SWIR imaging demonstrations have yet to move beyond two-color imaging schemes. In this study, we engineered a set of three high quantum yield lead sulfide/cadmium sulfide (PbS/CdS) core/shell QDs with distinct SWIR emissions ranging from 1100 - 1550 nm and utilize these for simultaneous three-color imaging in mice. We first use QDs to non-invasively track lymphatic drainage, highlighting the detailed network of lymphatic vessels with high-resolution with a widefield imaging over a 2 hr period. We then perform multiplexed imaging with all three QDs to distinctly visualize the lymphatic system and spatially overlapping vasculature network. This work establishes optimized SWIR QDs for next-generation multiplexed preclinical imaging, moving beyond the capability of previous dual-labeling techniques. The capacity to discriminate several fluorescent labels through non-invasive NIR-I excitation and SWIR detection unlocks numerous opportunities for studies of disease progression, drug biodistribution, and cell trafficking dynamics in living organisms.

Experimental Study on the Mechanical Properties of Disposable Mask Waste-Reinforced Gangue Concrete.

This paper is grounded on the following information: (1) Disposable masks primarily consist of polypropylene fiber, which exhibits excellent flexibility. (2) China has extensive coal gangue deposits that pose a significant environmental hazard. (3) Coal gangue concrete exhibits greater fragility compared to regular concrete and demonstrates reduced resistance to deformation. With the consideration of environmental conservation and resource reutilization, a preliminary concept suggests the conversion of discarded masks into fibers, which can be blended with coal gangue concrete to enhance its mechanical characteristics. In this paper, the stress-strain law of different mask fiber-doped coal gangue concrete (DMGC) under uniaxial compression is studied when the matrix strength is C20 and C30, and the effect of mask fiber content on the mechanical behavior and energy conversion relationship of coal gangue concrete is analyzed. The experimental results show that when the content of mask fiber is less than 1.5%, the strength, elastic modulus, deformation resistance, and energy dissipation of the concrete increase with mask fiber content. When the amount of mask fiber is more than 1.5%, because the tensile capacity and energy dissipation level of concrete produced by the mask fiber cannot compensate for the compression and deformation resistance of concrete of the same quantity and because excess fiber is difficult to evenly mix in the concrete, there are pore defects in concrete, which decreases the concrete strength due to the increase in mask fiber. Therefore, adding less than 1.5% mask fiber helps to improve the ductility, toughness, impermeability, and oxidation and control the cracking of coal gangue concrete. Based on Weibull theory, a constitutive model of DMGC is established, which fits well with the results of a uniaxial test, providing support for understanding the mechanical law of mask fiber-doped concrete.

Development of a Rapid Epstein-Barr Virus Detection System Based on Recombinase Polymerase Amplification and a Lateral Flow Assay.

The quality of cellular products used in biological research can directly impact the ability to obtain accurate results. Epstein-Barr virus (EBV) is a latent virus that spreads extensively worldwide, and cell lines used in experiments may carry EBV and pose an infection risk. The presence of EBV in a single cell line can contaminate other cell lines used in the same laboratory, affecting experimental results. We developed three EBV detection systems: (1) a polymerase chain reaction (PCR)-based detection system, (2) a recombinase polymerase amplification (RPA)-based detection system, and (3) a combined RPA-lateral flow assay (LFA) detection system. The minimum EBV detection limits were 1 × 103 copy numbers for the RPA-based and RPA-LFA systems and 1 × 104 copy numbers for the PCR-based system. Both the PCR and RPA detection systems were applied to 192 cell lines, and the results were consistent with those obtained by the EBV assay methods specified in the pharmaceutical industry standards of the People's Republic of China. A total of 10 EBV-positive cell lines were identified. The combined RPA-LFA system is simple to operate, allowing for rapid result visualization. This system can be implemented in laboratories and cell banks as part of a daily quality control strategy to ensure cell quality and experimental safety and may represent a potential new technique for the rapid detection of EBV in clinical samples.

TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1-1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer.

Nasal epithelial gene expression and total IgE in children and adolescents with asthma.

BACKGROUND: Little is known about nasal epithelial gene expression and total IgE in youth. OBJECTIVE: We aimed to identify genes whose nasal epithelial expression differs by total IgE in youth, and group them into modules that could be mapped to airway epithelial cell types. METHODS: We conducted a transcriptome-wide association study of total IgE in 469 Puerto Ricans aged 9 to 20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study, separately in all subjects and in those with asthma. We then attempted to replicate top findings for each analysis using data from 3 cohorts. Genes with a Benjamini-Hochberg-adjusted P value of less than .05 in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study and a P value of less than .05 in the same direction of association in 1 or more replication cohort were considered differentially expressed genes (DEGs). DEGs for total IgE in subjects with asthma were further dissected into gene modules using coexpression analysis, and such modules were mapped to specific cell types in airway epithelia using public single-cell RNA-sequencing data. RESULTS: A higher number of DEGs for total IgE were identified in subjects with asthma (n = 1179 DEGs) than in all subjects (n = 631 DEGs). In subjects with asthma, DEGs were mapped to 11 gene modules. The top module for positive correlation with total IgE was mapped to myoepithelial and mucus secretory cells in lower airway epithelia and was regulated by IL-4, IL5, IL-13, and IL-33. Within this module, hub genes included CDH26, FETUB, NTRK2, CCBL1, CST1, and CST2. Furthermore, an enrichment analysis showed overrepresentation of genes in signaling pathways for synaptogenesis, IL-13, and ferroptosis, supporting interactions between interleukin- and acetylcholine-induced responses. CONCLUSIONS: Our findings for nasal epithelial gene expression support neuroimmune coregulation of total IgE in youth with asthma.

A Safe Technique for Excising the Perpendicular Plate of the Ethmoid Bone in Patients with Crooked Nose: A Finite Element Analysis.

BACKGROUND: Correction of the crooked nose, especially the perpendicular plate of the ethmoid bone, has the potential to cause skull base injury. At present, the safe and effective method for perpendicular plate resection has not been clearly defined through biomechanics. METHOD: CT scan data of 48 patients with crooked nose and deviated nasal septum were divided into C-type, angular deformity-type, and S-type based on the morphology of the 3D model. Different types of finite element models of the nasal bony septum and skull base were established. The osteotomy depth, angle, and force mode of the PPE resection were simulated by assembling different working conditions for the models. The von Mises stress of the anterior cranial fossa was observed. RESULTS: When the osteotomy line length was 0.5 cm, the angle was at 30° to the Frankfurt plane, and 50 N·mm torque was applied, the von Mises stress of the skull base was minimal in the four models, showing 0.049 MPa (C-type), 0.082 MPa (S-type), 0.128 MPa (angular deformity-type), and 0.021 MPa (control model). The maximum von Mises stress values were found at the skull base when the osteotomy line was 1.5 cm, the angle was 50°, and the force was 10 N along the X-axis, showing 0.349 MPa (C-type), 0.698 MPa (S-type), 0.451 MPa (angular deformity-type), and 0.149 MPa (control model). CONCLUSION: The use of smaller resection angle with the Frankfurt plane, conservative resection depth, and torsion force can better reduce the stress value at the skull base and reduce the risk of basicranial fracture. It is a safe and effective technique for perpendicular plate resection of the ethmoid bone in the correction of crooked nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cu Tailoring Pt Enables Branched-Structured Electrocatalysts with High Concave Surface Curvature Toward Efficient Methanol Oxidation.

Surface engineering offers opportunities for the design and synthesis of Pt-based alloyed electrocatalysts with high mass activity and resistance to CO poisoning, which is of great significance for methanol electrooxidation. Surface curvature regulation may endow electrocatalysts with enhanced atomic utilization and abundance of unsaturated atoms; however, a reliable synthetic route for controlled construction of tailorable curved surface is still lacking. Here, a colloidal-chemical method to synthesize two types of PtCu branched-structured electrocatalysts, where the concave curvature can be customized is reported. These studies show that, among various synthesis parameters, the concentration of CuCl2 ·2H2 O precursor is the key factor in manipulating the reaction kinetics and determining the concave surface curvature. Significantly, PtCu branched nanocrystals with long and sharp arms (PtCu BNCs-L), featuring a high concave surface curvature, exhibit remarkable activity and stability toward MOR, which is mainly attributed to advanced features of a highly concave surface and the synergistically bifunctional effect from introduced oxophilic Cu metal. In situ Raman spectroscopy and CO stripping test demonstrates weakened CO adsorption and accelerated CO removal on PtCu BNCs-L. This work highlights the importance of surface curvature, opening up an appealing route for the design and synthesis of advanced electrocatalysts with well-defined surface configurations.

Smart Lipid Nanoparticle that Remodels Tumor Microenvironment for Activatable H2S Gas and Photodynamic Immunotherapy.

Hydrogen sulfide (H2S) has shown promise for gas therapy. However, it is still controversial whether H2S can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (1-JK-PS-FA) is presented, which is capable of delivering and releasing H2S specifically in tumor tissues for on-demand H2S gas and photodynamic immunotherapy. 1-JK-PS-FA enables a burst release of H2S in the acidic TME, which promptly reduces the embedded organic electrochromic materials and consequently switches on near-infrared fluorescence and photodynamic activity. Furthermore, we found that high levels of H2S can reprogram the TME by reducing tumor interstitial fluid pressure, promoting angiogenesis, increasing vascular permeability, ameliorating hypoxia, and reducing immunosuppressive conditions. This leads to increased tumor uptake of 1-JK-PS-FA, thereby enhancing PDT efficacy and eliciting strong immunogenic cell death during 808 nm laser irradiation. Therefore, 1-JK-PS-FA permits synergistic H2S gas and photodynamic immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence. This work showcases the capacity of H2S to reprogram the TME to enhance H2S gas and immunotherapy.

Development of a nutritional screening and assessment indicator system for patients with esophageal cancer in China: Findings from the Delphi method.

BACKGROUND: In China, individuals diagnosed with esophageal cancer are confronted with an elevated risk of nutritional inadequacy or malnutrition throughout the course of their disease, a condition that contributes to various adverse clinical outcomes. A vast corpus of data are burgeoning at an unprecedented rate, primarily due to the revolutionary growth of digitalization technologies and artificial intelligence, notably within the domains of health care and medicine. The purpose of this investigation is to initiate the development of a nutritional screening and assessment indicator framework for patients with esophageal cancer within the Chinese context. We seek to furnish an instrumental reference to facilitate preparations for the forthcoming era of advanced, "deep," evidence-based medicine. METHODS: An integrative methodology was employed to forge the preliminary draft of the nutritional screening and assessment indicator system for preoperative patients with esophageal cancer. This encompassed a rigorous literature survey, in-depth clinical practice investigation, and the facilitation of expert panel discussions. Thereafter, two iterative consultation phases were conducted using the Delphi method in China. The analytic hierarchy process was deployed to ascertain the weighting of each index within the definitive evaluation indicator system. RESULTS: The effective response rates for the dual rounds of expert consultation were 91.7% and 86.4%, with commensurate authority coefficients of 0.97 and 0.91. The Kendall harmony coefficients were ascertained to be 0.19 and 0.14 (p < 0.01), respectively. The culminating nutritional screening and assessment indicator system for patients with esophageal cancer comprised 5 primary-level indicators and 38 secondary-level indicators. CONCLUSIONS: The nutritional screening and assessment indicator system contrived for patients with esophageal cancer is underpinned by cogent theoretical principles, leverages an astute research methodology, and manifests dependable outcomes. This system may be appositely utilized as a meaningful reference for the nutritional screening and assessment process in patients afflicted with esophageal cancer.

MSL2 ensures biallelic gene expression in mammals.

In diploid organisms, biallelic gene expression enables the production of adequate levels of mRNA1,2. This is essential for haploinsufficient genes, which require biallelic expression for optimal function to prevent the onset of developmental disorders1,3. Whether and how a biallelic or monoallelic state is determined in a cell-type-specific manner at individual loci remains unclear. MSL2 is known for dosage compensation of the male X chromosome in flies. Here we identify a role of MSL2 in regulating allelic expression in mammals. Allele-specific bulk and single-cell analyses in mouse neural progenitor cells revealed that, in addition to the targets showing biallelic downregulation, a class of genes transitions from biallelic to monoallelic expression after MSL2 loss. Many of these genes are haploinsufficient. In the absence of MSL2, one allele remains active, retaining active histone modifications and transcription factor binding, whereas the other allele is silenced, exhibiting loss of promoter-enhancer contacts and the acquisition of DNA methylation. Msl2-knockout mice show perinatal lethality and heterogeneous phenotypes during embryonic development, supporting a role for MSL2 in regulating gene dosage. The role of MSL2 in preserving biallelic expression of specific dosage-sensitive genes sets the stage for further investigation of other factors that are involved in allelic dosage compensation in mammalian cells, with considerable implications for human disease.

C-type natriuretic peptide improves maternally aged oocytes quality by inhibiting excessive PINK1/Parkin-mediated mitophagy.

The overall oocyte quality declines with aging, and this effect is strongly associated with a higher reactive oxygen species (ROS) level and the resultant oxidative damage. C-type natriuretic peptide (CNP) is a well-characterized physiological meiotic inhibitor that has been successfully used to improve immature oocyte quality during in vitro maturation. However, the underlying roles of CNP in maternally aged oocytes have not been reported. Here, we found that the age-related reduction in the serum CNP concentration was highly correlated with decreased oocyte quality. Treatment with exogenous CNP promoted follicle growth and ovulation in aged mice and enhanced meiotic competency and fertilization ability. Interestingly, the cytoplasmic maturation of aged oocytes was thoroughly improved by CNP treatment, as assessed by spindle/chromosome morphology and redistribution of organelles (mitochondria, the endoplasmic reticulum, cortical granules, and the Golgi apparatus). CNP treatment also ameliorated DNA damage and apoptosis caused by ROS accumulation in aged oocytes. Importantly, oocyte RNA-seq revealed that the beneficial effect of CNP on aged oocytes was mediated by restoration of mitochondrial oxidative phosphorylation, eliminating excessive mitophagy. CNP reversed the defective phenotypes in aged oocytes by alleviating oxidative damage and suppressing excessive PINK1/Parkin-mediated mitophagy. Mechanistically, CNP functioned as a cAMP/PKA pathway modulator to decrease PINK1 stability and inhibit Parkin recruitment. In summary, our results demonstrated that CNP supplementation constitutes an alternative therapeutic approach for advanced maternal age-related oocyte deterioration and may improve the overall success rates of clinically assisted reproduction in older women.

An integrated analysis identifies six molecular subtypes of pancreatic ductal adenocarcinoma revealing cellular and molecular landscape.

Pancreatic ductal adenocarcinoma (PDA) has been found to have a high mortality rate. Despite continuous efforts, current histopathological classification is insufficient to guide individualized therapies of PDA. We first define the molecular subtypes of PDA (MSOP) based on a meta-cohort of 845 samples from 11 PDA datasets. We then performed functional analyses involving immunity, fibrosis and metabolism. We recognized six molecular subtypes with different survival statistics and molecular composition. The squamous basal-like (SBL) subtype had a poor prognosis and high infiltration of ENO1+ (Enolase 1)/ADM+ (Adrenomedullin) cancer-associated fibroblasts (CAFs). The immune mesenchymal-like (IML) subtype and the normal mesenchymal-like (NML) subtype were characterized by genes associated with extracellular matrix (ECM) activities and immune responses, having favorable prognoses. IML was featured by elevated exhausted immune signaling and inflammatory CAFs infiltration, whereas NML was featured with myofibroblastic CAFs infiltration. The exocrine-like (EL) subtype was high in exocrine signals, while the pure classical-like (PCL) subtype lacked immunocytes infiltration. The quiescent-like (QL) subtype had diminished metabolic signaling and high infiltration of NK cells. SBL, IML and NML were enriched in innate anti-PD-1 resistance signatures. In sum, this MSOP depicts a vivid cell-to-molecular atlas of the tumor microenvironment of PDA and might facilitate to design a precise combination of therapies that target immunity, metabolism and stroma.

Maintenance anlotinib improves the survival prognosis of extensive-stage small cell lung cancer: a single-arm, prospective, phase II study.

The extent to which anlotinib provides survival benefits in the maintenance therapy of extensive-stage small cell lung cancer (ES-SCLC) remains unclear. Thus, this study aimed to assess the efficacy and safety of anlotinib monotherapy as maintenance therapy following induction chemotherapy in ES-SCLC patients. 27 ES-SCLC patients registered at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were screened from February 2022 to October 2022, of which 3 were not eligible. Eligible patients in stable status after first-line chemotherapy would subsequently accept oral anlotinib (12 mg, p.o., qd. on d1-d14, every 21 days). The maintenance method was continued until disease progression or unmanageable toxicity occurred. The primary endpoint is median progression-free survival (mPFS). The second endpoints include median duration of response (mDOR), median overall survival (mOS) and safety. The mPFS and mDOR have been determined (mPFS: 252 days, 95% CI: 217.782-286.218 days; mDOR: 126 days, 95% CI: 98.899-153.101 days). The mOS was not reached; only 7 patients were reached while 20 patients survived. The primary treatment-related adverse events included hypertension (n=7, 25.9%), fatigue (n=5, 18.5%), poor appetite (n=5, 18.5%), and others. Notably, no patients required a dose reduction due to the severity of adverse events. Patients were generally able to tolerate treatment with anlotinib and exhibited a favorable prognosis. Anlotinib achieved prospective efficacy and manageable safety in the maintenance treatment of ES-SCLC.

The Morphological and Functional Effects of the Endoscope-Assisted One-Stage Approach for Crooked Nose.

BACKGROUND: A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems. METHODS: The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring. RESULTS: For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the "nasal obstruction symptom evaluation "score of patients were both significantly improved ( t = -7.508 and t =6.310, respectively, P < 0.001). CONCLUSION: Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.

The NSL complex is required for piRNA production from telomeric clusters.

The NSL complex is a transcriptional activator. Germline-specific knockdown of NSL complex subunits NSL1, NSL2, and NSL3 results in reduced piRNA production from a subset of bidirectional piRNA clusters, accompanied by widespread transposon derepression. The piRNAs most transcriptionally affected by NSL2 and NSL1 RNAi map to telomeric piRNA clusters. At the chromatin level, these piRNA clusters also show decreased levels of H3K9me3, HP1a, and Rhino after NSL2 depletion. Using NSL2 ChIP-seq in ovaries, we found that this protein specifically binds promoters of telomeric transposons HeT-A, TAHRE, and TART Germline-specific depletion of NSL2 also led to a reduction in nuclear Piwi in nurse cells. Our findings thereby support a role for the NSL complex in promoting the transcription of piRNA precursors from telomeric piRNA clusters and in regulating Piwi levels in the Drosophila female germline.

Effects of Dietary Chenodeoxycholic Acid Supplementation in a Low Fishmeal Diet Containing Clostridium autoethanogenum Protein on Growth, Lipid and Cholesterol Metabolism, and Hepatopancreas Health of Litopenaeus vannamei.

The study aimed to assess the impact of adding chenodeoxycholic acid (CDCA) to the diet of Litopenaeus vannamei on their growth performance, lipid and cholesterol metabolism, and hepatopancreas health while being fed a low fishmeal diet. Five diets were formulated, one of which contained 25% fishmeal (PC); fishmeal was partially replaced with Clostridium autoethanogenum protein in the remaining four diets and supplemented with 0, 0.03, 0.06, and 0.09% CDCA (NC, BA1, BA2, and BA3, respectively). In this study, four replicates of each diet were assigned and each replicate consisted of 30 shrimp with an average weight of (0.25 ± 0.03 g). The shrimp were fed four times a day for a period of 56 days. The results of this study indicate that the inclusion of CDCA in the diet had a positive impact on the growth performance of the shrimp. The final body weight (FBW), weight gain (WG), and specific growth rate (SGR) of the shrimp in the PC group were similar to those in the BA2 group, and significantly higher than those in the other three groups. The survival rate (SR) was similar among all groups. In comparison to the PC group, the low fishmeal groups exhibited a significant decrease in the crude lipid content of the whole shrimp, as well as the Total cholesterol (T-CHOL), Low-density lipoprotein (LDL-C), and High-density lipoprotein (HDL-C) levels in the hemolymph. Regarding the sterol metabolism, the dietary supplementation of CDCA up-regulated the mRNA expression of intracellular cholesterol transporter 1-like (npc1), 7-dehydrocholesterol reductase (7dhcr), Delta (24) sterol reductase (Δ24), HMG-CoA reductase membrane form (hmgcr), and sterol carrier protein 2 (scp). In the lipid metabolism, the mRNA expression of sterol-regulatory element binding protein (srebp) was significantly down-regulated in the shrimp fed the BA1 diet and the expression of AMP-activated protein kinase (ampk) was significantly up-regulated in the shrimp fed the BA1 and BA3 diets compared to the PC group. The mRNA expression of triacylglycerol lipase (tgl) was significantly up-regulated in the shrimp fed the BA2 diet compared to the NC group. Compared with the shrimp fed the PC diets, the dietary supplementation of CDCA significantly down-regulated the protein expression of SREBP1. The lumen damage in the BA1 group was significantly less severe than those in the NC group. The addition of 0.06% CDCA to low fishmeal diets can improve the growth performance, lipid and cholesterol metabolism, and hepatopancreas health of L. vannamei.

Successful replantation of amputated facial tissues by supermicrosurgery.

BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.