The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Health-related quality of life measurements in children and adolescents with refractive errors: A scoping review.

Background: Refractive errors, particularly myopia, are the leading visual disorders worldwide, significantly affecting the quality of life (QOL) even after correction. This scoping review focuses on health-related quality of life (HRQOL) measurements for children and adolescents with refractive errors. Main text: We explored generic and disease-specific HRQOL tools, examining their content, psychometric properties, and the impact of various interventions on QOL. Two English databases-PubMed, Embase, and one Chinese database, CNKI, were searched for relevant studies published from January 2001 to October 2023. Inclusion criteria encompassed studies using standardized instruments to assess the QOL of children aged 0-18 with refractive errors. The review compares prevalent HRQOL measurements, analyzes children's refractive error assessments, and discusses intervention effects on patient QOL. Conclusions: The study underlines the necessity of developing disease-specific QOL instruments for very young children and serves as a practical guide for researchers in this field. The findings advocate for a targeted approach in HRQOL assessment among the pediatric population, identifying critical gaps in current methodologies.

Association Between Hemoglobin-Albumin-Lymphocyte-Platelet Index and Mortality in Hospitalized COVID-19 Omicron BA.2 Infected Patients.

Background: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated. Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People's Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan-Meier curves, Cox regression models, interaction, and stratified analyses. Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17-3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥70 (HR = 2.22, CI = 1.18-4.15) and severe cases (HR = 2.09, CI = 1.13-3.86). Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.

Comparing the morphology of optic nerve head and lamina cribrosa in full-term and preterm school-aged children.

OBJECTIVES: To evaluate the morphology of lamina cribrosa (LC) in preterm school-aged children. METHODS: A study of 120 eyes from 120 patients, including 42 full-term children (control group), 41 preterm children without retinopathy of prematurity (ROP), 16 children with ROP treated with intravitreal bevacizumab (IVB), and 21 children with ROP treated with laser. Five parameters of LC were measured by optical coherence tomography, including Bruch's membrane opening (BMO) diameter, minimum rim width (MRW), LC depth, prelaminar tissue (PLT) thickness, and LC curvature index (LCCI). RESULTS: The PLT thickness increased with age in full-term and preterm children (ß = 30.1, P = 0.003 and ß = 19.6, P < 0.001, respectively). LC depth and LCCI showed no differences between full-term and preterm children. Worse refractive errors in preterm children were associated with greater MRW and PLT thickness (ß = -17.1, P = 0.001 and ß = -5.7, P = 0.03, respectively). However, this relationship was not found in full-term children. Laser-treated children had greater MRW, PLT, temporal peripapillary retinal nerve fibre layer, and foveal thickness than full-term or other preterm children (all P < 0.05). CONCLUSIONS: Prematurity and ROP treatment may have an impact on the structural development of the LC. Refractive status plays a vital role in the LC structure of preterm children. This highlights the refractive errors of preterm children at school age that merit greater attention.

Therapeutic effects of deep pharyngeal electrical stimulation combined with modified masako maneuver on aspiration in patients with stroke.

BACKGROUND: Stroke patients often experience difficulty swallowing. OBJECTIVE: To assist in the improvement of dysphagia symptoms by introducing a novel approach to the treatment of patients with post-stroke aspiration. METHODS: A total of 60 patients with post-stroke aspiration were enrolled and divided into an experimental group (n = 30) and a control group (n = 30). The control group received standard treatment, sham intraoral stimulation, and the Masako maneuver, while the experimental group was administered standard treatment, deep pharyngeal electrical stimulation (DPES), and a modified Masako maneuver. Changes in their Functional Oral Intake Scale (FOIS) and Rosenbek scale scores were observed. RESULTS: The FOIS scores of both groups increased significantly after treatment (p <  0.01, respectively). The Rosenbek scale scores of both groups decreased significantly after treatment, with the experimental group scoring significantly lower than the control group (1.01±0.09 vs. 2.30±0.82) (p <  0.05). After treatment, the overall response rate in the experimental group (93.33%) was significantly higher than that in the control group (83.33%) (p <  0.001). CONCLUSION: In terms of effectively improving dysphagia in aspiration patients after stroke, DPES combined with modified Masako maneuver is clinically recommended.

Ionic Liquid Pretreatment Enhances Skin Penetration of 5-Aminolevulinic Acid: A Promising Scheme for Photodynamic Therapy for Acne Vulgaris.

Acne vulgaris is one of the most prevalent skin disorders; it affects up to 85% of adolescents and often persists into adulthood. Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides an alternative treatment for acne; however, its efficacy is greatly undermined by the limited skin permeability of ALA. Herein, biocompatible ionic liquids (ILs) based on aliphatic acid/choline were employed to enhance the dermal delivery of ALA, thereby improving the efficacy of PDT. In addition to the one-step delivery of ALA by utilizing ILs as carriers, a two-step strategy of pretreating the skin with blank ILs, followed by the administration of free ALA, was employed to test the IL-facilitated dermal delivery of ALA in vitro. The cumulative permeation of ALA through the excised rat skin after IL pretreatment was significantly greater than that in the untreated group, the 20% dimethyl sulfoxide (DMSO) penetration enhancer group, and the one-step group. The penetration efficiency was influenced by formulation and treatment factors, including the type of IL, pretreatment duration, water content in the ILs, and concentration of ALA. In rats, IL pretreatment facilitated faster, greater, and deeper ALA-induced protoporphyrin IX (PpIX) accumulation. Moreover, the IL pretreatment regimen significantly improved the efficacy of ALA-based PDT against acne vulgaris in a rat ear model. The model IL choline citrate ([Ch]3[Cit]1) had a moderate effect on the skin barrier. Trans-epidermal water loss could be recovered 1 h after IL treatment, but no irritation to the rat skin was detected after 7 days of consecutive treatment. It was concluded that biocompatible IL pretreatment enhances the penetration of ALA and thus facilitates the transformation of PpIX and improves the efficacy of PDT against acne vulgaris.

Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway.

BACKGROUND: Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. PURPOSE: To evaluate the efficacy and mechanism of Geniposide in treating AS. STUDY DESIGN AND METHODS: Geniposide was administered to high-fat diet-fed ApoE-/- mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. RESULTS: In vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. CONCLUSION: Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.

Solvent-free selective hydrogenation of nitroaromatics to azoxy compounds over Co single atoms decorated on Nb2O5 nanomeshes.

The solvent-free selective hydrogenation of nitroaromatics to azoxy compounds is highly important, yet challenging. Herein, we report an efficient strategy to construct individually dispersed Co atoms decorated on niobium pentaoxide nanomeshes with unique geometric and electronic properties. The use of this supported Co single atom catalysts in the selective hydrogenation of nitrobenzene to azoxybenzene results in high catalytic activity and selectivity, with 99% selectivity and 99% conversion within 0.5 h. Remarkably, it delivers an exceptionally high turnover frequency of 40377 h-1, which is amongst similar state-of-the-art catalysts. In addition, it demonstrates remarkable recyclability, reaction scalability, and wide substrate scope. Density functional theory calculations reveal that the catalytic activity and selectivity are significantly promoted by the unique electronic properties and strong electronic metal-support interaction in Co1/Nb2O5. The absence of precious metals, toxic solvents, and reagents makes this catalyst more appealing for synthesizing azoxy compounds from nitroaromatics. Our findings suggest the great potential of this strategy to access single atom catalysts with boosted activity and selectivity, thus offering blueprints for the design of nanomaterials for organocatalysis.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Progress in Biological Research and Treatment of Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with excellent efficacy and safety, and is associated with breakthrough progress in long-term disease control and prolonged survival. However, the high recurrence rate of PMP is the key challenge in its treatment, which limits the clinical application of multiple rounds of CRS-HIPEC and does not benefit from conventional systemic chemotherapy. Therefore, the development of alternative therapies for patients with refractory or relapsing PMP is critical. The literature related to PMP research progress and treatment was searched in the Web of Science, PubMed, and Google Scholar databases, and a literature review was conducted. The overview of the biological research, treatment status, potential therapeutic strategies, current research limitations, and future directions associated with PMP are presented, focuses on CRS-HIPEC therapy and alternative or combination therapy strategies, and emphasizes the clinical transformation prospects of potential therapeutic strategies such as mucolytic agents and targeted therapy. It provides a theoretical reference for the treatment of PMP and the main directions for future research.

Tribological Behavior of Sulfonated Polyether Ether Ketone with Three Different Chemical Structures under Water Lubrication.

With the development of the shipbuilding industry, it is necessary to improve tribological properties of polyether ether ketone (PEEK) as a water-lubricated bearing material. In this study, the sulfonated PEEK (SPEEK) with three distinct chemical structures was synthesized through direct sulfonated polymerization, and high fault tolerance and a controllable sulfonation degree ensured the batch stability. The tribological and mechanical properties of SPEEK with varying side groups (methyl and tert-butyl) and rigid segments (biphenyl) were compared after sintering in a vacuum furnace. Compared to the as-made PEEK, as the highly electronegative sulfonic acid group enhanced the hydration lubrication, the friction coefficient and wear rate of SPEEK were significantly reduced by 30% and 50% at least without affecting the mechanical properties. And lower steric hindrance and entanglement between molecular chains were proposed to be partially responsible for the lowest friction behavior of SPEEK with methyl side groups, making it a promising and competitive option for water-lubricated bearings.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

Effects of warming on rice production and metabolism process associated with greenhouse gas emissions.

Evaluating the impact of global warming on rice production and greenhouse gas (GHG) emissions is critical for ensuring food security and mitigating the consequences of climate change. Nonetheless, the impacts of warming on crop production, GHG emissions, and microbial mechanisms in the single-cropping rice systems remain unclear. Here, a two-year field experiment was conducted to explore the effects of warming (increased by 2.7-3.0 °C on average) in the rice growing season on crop production and functional microorganisms associated with GHG emissions. Results showed that warming resulted in significant reduction (p < 0.01) in the aboveground biomass and grain yield as well as in grain weight, the number of spikelets per panicle, and the seed-setting rate. However, it caused a significant increase (p < 0.01) in the number of panicles by 15.6 % and 34.9 %, respectively. Furthermore, warming significantly increased (p < 0.01) seasonal methane (CH4) emissions but reduced nitrous oxide (N2O) emissions, particularly in 2022.The relative abundance of genes associated with CH4 metabolism and nitrogen metabolism was increased by 40.7 % and 32.7 %, respectively, in response to warming. Moreover, warming had a positive impact on the abundance of genes related to CH4 production and oxidation processes but did not affect the denitrification processes associated with N2O production. These results showed that warming decreased rice yield and biomass in the single cropping rice system but increased CH4 emissions and global warming potential. Taken together, to address the increasing food demand of a growing population and mitigate the impacts of global warming, it is imperative to duce GHG emissions and enhance crop yields.

[Identification and functional analysis of jasmonic acid signaling repressor McJAZ8 gene in Mentha canadensis].

Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.

[Cloning and expression pattern analysis of abscisic acid receptor gene McPYL4 in Mentha canadensis].

Mentha canadensis is a traditional Chinese herb with great medicinal and economic value. Abscisic acid(ABA) receptor PYLs have important roles in plant growth and development and response to adversity. The M. canadensis McPYL4 gene was cloned, and its protein characteristics, gene expression, and protein interactions were analyzed, so as to provide genetic resources for genetic improvement and molecular design breeding for M. canadensis resistance. Therefore, the protein characteristics, subcellular localization, gene expression pattern, and protein interactions of McPYL4 were analyzed by bioinformatics analysis, transient expression of tobacco leaves, RT-qPCR, and yeast two-hybrid(Y2H) techniques. The results showed that the McPYL4 gene was 621 bp in length, encoding 206 amino acids, and its protein had the conserved structural domain of SRPBCC and was highly homologous with Salvia miltiorrhiza SmPYL4. McPYL4 protein was localized to the cell membrane and nucleus. The McPYL4 gene was expressed in all tissue of M. canadensis, with the highest expression in roots, followed by leaves, and it showed a pattern of up-regulation followed by down-regulation in leaves 1-8. In both leaves and roots, the McPYL4 gene responded to the exogenous hormones ABA, MeJA, and the treatments of drought, AlCl_3, NaCl, CdCl_2, and CuCl_2. Moreover, McPYL4 was up-regulated for expression in both leaves and roots under the MeJA treatment, as well as in leaves treated with AlCl_3 stress for 1 h, whereas McPYL4 showed a tendency to be down-regulated in both leaves and roots under other treatments. Protein interactions showed that McPYL4 interacted with AtABI proteins in an ABA-independent manner. This study demonstrated that McPYL4 responded to ABA, JA, and several abiotic stress treatments, and McPYL4 was involved in ABA signaling in M. canadensis and thus in the regulation of leaf development and various abiotic stresses in M. canadensis.

mTOR Inhibition Prolongs Survival and Has Beneficial Effects on Heart Function After Onset of Lamin A/C Gene Mutation Cardiomyopathy in Mice.

BACKGROUND: Mutations in LMNA encoding nuclear envelope proteins lamin A/C cause dilated cardiomyopathy. Activation of the AKT/mTOR (RAC-α serine/threonine-protein kinase/mammalian target of rapamycin) pathway is implicated as a potential pathophysiologic mechanism. The aim of this study was to assess whether pharmacological inhibition of mTOR signaling has beneficial effects on heart function and prolongs survival in a mouse model of the disease, after onset of heart failure. METHODS: We treated male LmnaH222P/H222P mice, after the onset of heart failure, with placebo or either of 2 orally bioavailable mTOR inhibitors: everolimus or NV-20494, a rapamycin analog highly selective against mTORC1. We examined left ventricular remodeling, and the cell biological, biochemical, and histopathologic features of cardiomyopathy, potential drug toxicity, and survival. RESULTS: Everolimus treatment (n=17) significantly reduced left ventricular dilatation and increased contractility on echocardiography, with a 7% (P=0.018) reduction in left ventricular end-diastolic diameter and a 39% (P=0.0159) increase fractional shortening compared with placebo (n=17) after 6 weeks of treatment. NV-20494 treatment (n=15) yielded similar but more modest and nonsignificant changes. Neither drug prevented the development of cardiac fibrosis. Drug treatment reactivated suppressed autophagy and inhibited mTORC1 signaling in the heart, although everolimus was more potent. With regards to drug toxicity, everolimus alone led to a modest degree of glucose intolerance during glucose challenge. Everolimus (n=20) and NV-20494 (n=20) significantly prolonged median survival in LmnaH222P/H222P mice, by 9% (P=0.0348) and 11% (P=0.0206), respectively, compared with placebo (n=20). CONCLUSIONS: These results suggest that mTOR inhibitors may be beneficial in patients with cardiomyopathy caused by LMNA mutations and that further study is warranted.

Self-assembled peptide nanotubes (SPNTs)/SnO2 nanocomposites for high-performance NO2 sensing at room temperature.

Nitrogen dioxide (NO2) is a major pollutant that poses significant risks to sustainable human life. As a result, a growing focus has been placed on the development of highly selective and sensitive gas sensors for NO2. Traditional cutting-edge non-organic NO2 gas detectors often necessitate stringent production conditions and potentially harmful materials, which are not environmentally friendly, and these shortcomings have limited their widespread practical use. To overcome these challenges, we synthesized self-assembled peptide nanotubes (SPNTs) through a molecular self-assembly process. The SPNTs were then combined with SnO2 in varying proportions to construct NO2 gas sensors. The design of this sensor ensured efficient electron transfer and leverage the extensive surface area of the SPNTs for enhanced gas adsorption and the effective dispersion of SnO2 nanoparticles. Notably, the performance of the sensor, including its sensitivity, response time, and recovery rate, along with a lower detection threshold, could be finely tuned by varying the SPNTs content. This approach illustrated the potential of bioinspired methodologies, using peptide self-assemblies, to develop integrated sensors for pollutant detection, providing a significant development in environmentally conscious sensor technology.

Effects of Klebsiella michiganensis LDS17 on Codonopsis pilosula growth, rhizosphere soil enzyme activities, and microflora, and genome-wide analysis of plant growth-promoting genes.

Codonopsis pilosula is a perennial herbaceous liana with medicinal value. It is critical to promote Codonopsis pilosula growth through effective and sustainable methods, and the use of plant growth-promoting bacteria (PGPB) is a promising candidate. In this study, we isolated a PGPB, Klebsiella michiganensis LDS17, that produced a highly active 1-aminocyclopropane-1-carboxylate deaminase from the Codonopsis pilosula rhizosphere. The strain exhibited multiple plant growth-promoting properties. The antagonistic activity of strain LDS17 against eight phytopathogenic fungi was investigated, and the results showed that strain LDS17 had obvious antagonistic effects on Rhizoctonia solani, Colletotrichum camelliae, Cytospora chrysosperma, and Phomopsis macrospore with growth inhibition rates of 54.22%, 49.41%, 48.89%, and 41.11%, respectively. Inoculation of strain LDS17 not only significantly increased the growth of Codonopsis pilosula seedlings but also increased the invertase and urease activities, the number of culturable bacteria, actinomycetes, and fungi, as well as the functional diversity of microbial communities in the rhizosphere soil of the seedlings. Heavy metal (HM) resistance tests showed that LDS17 is resistant to copper, zinc, and nickel. Whole-genome analysis of strain LDS17 revealed the genes involved in IAA production, siderophore synthesis, nitrogen fixation, P solubilization, and HM resistance. We further identified a gene (koyR) encoding a plant-responsive LuxR solo in the LDS17 genome. Klebsiella michiganensis LDS17 may therefore be useful in microbial fertilizers for Codonopsis pilosula. The identification of genes related to plant growth and HM resistance provides an important foundation for future analyses of the molecular mechanisms underlying the plant growth promotion and HM resistance of LDS17. IMPORTANCE: We comprehensively evaluated the plant growth-promoting characteristics and heavy metal (HM) resistance ability of the LDS17 strain, as well as the effects of strain LDS17 inoculation on the Codonopsis pilosula seedling growth and the soil qualities in the Codonopsis pilosula rhizosphere. We conducted whole-genome analysis and identified lots of genes and gene clusters contributing to plant-beneficial functions and HM resistance, which is critical for further elucidating the plant growth-promoting mechanism of strain LDS17 and expanding its application in the development of plant growth-promoting agents used in the environment under HM stress.

Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS.

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

Analysis of risk factors and development of a nomogram-based prediction model for defective bony non-union.

Objective: To explore risk factors for defective non-union of bone and develop a nomogram-based prediction model for such an outcome. Methods: This retrospective study analysed the case data of patients with defective bony non-unions who were treated at the authors' hospital between January 2010 and December 2020. Patients were divided into the union and non-union groups according to their Radiographic Union Score for Tibia scores 1 year after surgery. Univariate analysis was performed to assess factors related to demographic characteristics, laboratory investigations, surgery, and trauma in both groups. Subsequently, statistically significant factors were included in the multivariate logistic regression analysis to identify independent risk factors. A nomogram-based prediction model was established using statistically significant variables in the multivariate analysis. The accuracy and stability of the model were evaluated using receiver operating characteristic (ROC) and calibration curves. The clinical applicability of the nomogram model was evaluated using decision curve analysis. Results: In total, 204 patients (171 male, 33 female; mean [±SD] age, 39.75 ± 13.00 years) were included. The mean body mass index was 22.95 ± 3.64 kg/m2. Among the included patients, 29 were smokers, 18 were alcohol drinkers, and 21 had a previous comorbid systemic disease (PCSD). Univariate analysis revealed that age, occupation, PCSD, smoking, drinking, interleukin-6, C-reactive protein (CRP), procalcitonin, alkaline phosphatase, glucose, and uric acid levels; blood calcium ion concentration; and bone defect size (BDS) were correlated with defective bone union (all P < 0.05). Multivariate logistic regression analysis revealed that PCSD, smoking, interleukin-6, CRP, and glucose levels; and BDS were associated with defective bone union (all P < 0.05), and the variables in the multivariate analysis were included in the nomogram-based prediction model. The value of the area under the ROC curve for the predictive model for bone defects was 0.95. Conclusion: PCSD, smoking, interleukin-6, CRP, and glucose levels; and BDS were independent risk factors for defective bony non-union, and the incidence of such non-union was predicted using the nomogram. These findings are important for clinical interventions and decision-making.