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Abstract Background Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. Methods This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. Results Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). Conclusions Sirolimus’s long-term administration is not associated with adverse effects on children’s physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. Trial registration Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. Methods A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. Results Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR

Abstract Background Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. Methods This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. Results The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn’t affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. Conclusions RFID tag witnessing doesn’t negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist’s confidence.

Abstract Background Cysticercosis is a zoonotic parasitic disease that poses a serious threat to public health. It is widely distributed and has a high incidence rate in China. Reports of disseminated cysticercosis worldwide are rare. This article presents a case of disseminated cysticercosis in the Guangxi Zhuang Autonomous Region of southwestern China. Case presentation The patient, a 46-year-old male belonging to the Miao ethnic group, hailed from a region in Guangxi Zhuang Autonomous Region known for its high incidence of cysticercosis. He had a habit of consuming raw pork and beef. With a history of recurrent consciousness disturbances and limb convulsions for five years, he presented with headaches and dizziness nine days prior. Comprehensive examinations were conducted on the patient. Ultimately, based on epidemiological history, imaging findings, pathogen testing, and pathological results, he was diagnosed with disseminated cysticercosis. Following anthelmintic treatment, the patient was discharged with clear consciousness, free from headaches, dizziness, nausea, vomiting, and seizures. The patient is currently under follow-up care. Conclusion It is crucial to enhance public awareness, promote health education, and cultivate good hygiene habits, as these are essential measures in reducing the incidence of cysticercosis.

Abstract Independent controls of various properties of electromagnetic (EM) waves are crucially required in a wide range of applications. Programmable metasurface is a promising candidate to provide an advanced platform for manipulating EM waves. Here, we propose an approach that can arbitrarily control the polarization direction and phases of reflected waves in linear and nonlinear ways using a stacked programmable metasurface. Further, we extend the space-time-coding theory to incorporate the dimension of polarization, which provides an extra degree of freedom for manipulating EM waves. As proof-of-principle application examples, we consider polarization rotation, phase manipulation, and beam steering at linear and nonlinear frequencies. For validation, we design, fabricate, and measure a metasurface sample. The experimental results show good agreement with theoretical predictions and simulations. The proposed approach has a wide range of applications in various areas, such as imaging, data storage, and wireless communication.

To overcome the limitations of geography, climate, and ore characteristics on the ore beneficiation process, bio-oxidation studies on low-grade arsenic-bearing refractory gold ore by pool leaching were carried out, as well as process fitting analysis. The gold particles are encapsulated by pyrite and arsenopyrite. After 60 days of bio-oxidation, the oxidation rates of arsenic, sulfur, and gold were 39%∼69%, 24%∼41%, and 49%∼83%, respectively. The inoculated Acidithiobacillus ferrooxidans, Ferroplasma acidiphilum, and Leptospirillum ferrodiazotrophum could all mediate the initial pyrite/arsenopyrite oxidation and the Fe2+ oxidation reaction, but only the former could mediate the subsequent sulfur compound oxidation. When compared to daily bacterial circulation and bacterial replacement every ten days, aeration improved the gold leaching rate by 14%∼22%. The Boltzmann model could fit both the arsenic and sulfur bio-oxidation, with model fit variances greater than 0.98. Based on the experimental and fitting results, the bio-oxidation cycle was determined to be 60 days, and the bio-oxidation mechanisms are summarized. This study has significant practical implications for the rational utilization of gold resources and provides theoretical and practical guidance for similar gold ores.

Abstract Background In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet’s-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. Case presentation Here, we report a rare case of Behcet’s-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet’s-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. Conclusions In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Abstract A novel Fe2Mo3O8/MoO2@MoS2 nanocomposite is synthesized for extremely sensitive detection of NH3 in the breath of kidney disease patients at room temperature. Compared to MoS2, α‐Fe2O3/MoS2, and MoO2@MoS2, it shows the optimal gas‐sensing performance by optimizing the formation of Fe2Mo3O8 at 900 °C. The annealed Fe2Mo3O8/MoO2@MoS2 nanocomposite (Fe2Mo3O8/MoO2@MoS2‐900 °C) sensor demonstrates a remarkably high selectivity of NH3 with a response of 875% to 30 ppm NH3 and an ultralow detection limit of 3.7 ppb. This sensor demonstrates excellent linearity, repeatability, and long‐term stability. Furthermore, it effectively differentiates between patients at varying stages of kidney disease through quantitative NH3 measurements. The sensing mechanism is elucidated through the analysis of alterations in X‐ray photoelectron spectroscopy (XPS) signals, which is supported by density functional theory (DFT) calculations illustrating the NH3 adsorption and oxidation pathways and their effects on charge transfer, resulting in the conductivity change as the sensing signal. The excellent performance is mainly attributed to the heterojunction among MoS2, MoO2, and Fe2Mo3O8 and the exceptional adsorption and catalytic activity of Fe2Mo3O8/MoO2@MoS2‐900 °C for NH3. This research presents a promising new material optimized for detecting NH3 in exhaled breath and a new strategy for the early diagnosis and management of kidney disease.

Individual tree detection and counting in unmanned aerial vehicle (UAV) imagery constitute a vital and practical research field. Vegetation remote sensing captures large-scale trees characterized by complex textures, significant growth variations, and high species similarity within the vegetation, which presents significant challenges for annotation and detection. Existing methods based on bounding boxes have struggled to convey semantics information about tree crowns. This paper proposes a novel deep learning network called VrsNet based on the density map information. The proposed work pioneers the segmentation and counting application by utilizing the semantic information of Gaussian contour. Besides, we sample and create the UAV vegetation remote sensing density dataset TreeFsc for experiments. In quantitative comparison across multiple datasets, the proposed method demonstrates high performance, with a 3.45 increase in MAE and a 4.75 increase in RMSE. Experiments demonstrate superior cross-region, cross-scale, and cross-species target detection capabilities of the proposed approach compared with the existing object detection methods. Our code and dataset are available at: https://github.com/luotiger123/VrsNet/tree/main/VrsNet.

Abstract Background Pickled mustard, the largest cultivated vegetable in China, generates substantial waste annually, leading to significant environmental pollution due to challenges in timely disposal, leading to decomposition and sewage issues. Consequently, the imperative to address this concern centers on the reduction and comprehensive resource utilization of raw mustard waste (RMW). To achieve complete and quantitative resource utilization of RMW, this study employs novel technology integration for optimizing its higher-value applications. Results Initially, subcritical hydrothermal technology was applied for rapid decomposition, with subsequent ammonia nitrogen removal via zeolite. Thereafter, photosynthetic bacteria, Rhodopseudomonas palustris, were employed to maximize hydrogen and methane gas production using various fermentation enhancement agents. Subsequent solid-liquid separation yielded liquid fertilizer from the fermented liquid and soil amendment from solid fermentation remnants. Results indicate that the highest glucose yield (29.6 ± 0.14) was achieved at 165–173℃, with a total sugar content of 50.2 g/L and 64% glucose proportion. Optimal ammonia nitrogen removal occurred with 8 g/L zeolite and strain stable growth at 32℃, with the highest OD600 reaching 2.7. Several fermentation promoters, including FeSO4, Neutral red, Na2S, flavin mononucleotide, Nickel titanate, Nickel oxide, and Mixture C, were evaluated for hydrogen production. Notably, Mixture C resulted in the maximum hydrogen production (756 mL), a production rate of 14 mL/h, and a 5-day stable hydrogen production period. Composting experiments enhanced humic acid content and organic matter (OM) by 17% and 15%, respectively. Conclusions This innovative technology not only expedites RMW treatment and hydrogen yield but also substantially enriches soil fertility. Consequently, it offers a novel approach for low-carbon, zero-pollution RMW management. The study’s double outcomes extend to large-scale RMW treatment based on the aim of full quantitative resource utilization of RMW. Our method provides a valuable reference for waste management in similar perishable vegetable plantations.

Abstract Radiotherapy (RT) is one of the important treatment modalities for non-small cell lung cancer (NSCLC). However, the maximum radiation dose that NSCLC patient can receive varies little. Therefore, the exploitation of novel RT sensitization approaches is a critical need for the clinical treatment. RT resistance in NSCLC is linked to tumor microenvironment (TME) hypoxia, cell cycle arrest and associated genetic alterations. Here, we designed a novel method for targeted delivery of quercetin (QT) and CeO2 to enhance RT sensitivity. We loaded QT into CeO2@ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO2 targeted to NSCLC tumors. Under the protection and targeted delivery of Zeolitic Imidazolate Framework-8 (ZIF-8), the nanocomplexes exhibited excellent catalytic mimetic activity in decomposing H2O2 into O2, thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO2@ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO2@ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC.

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.

ABSTRACTBreast cancer was considered as a kind of prone breast tumors with the complicated pathological mechanisms and diverse clinical classifications. In the clinical treatments of HER2-positive tumor patients, HER2 monoclonal antibodies, such as Herceptin, have shown well-defined therapeutic effects. Nevertheless, due to the heterogeneity of breast cancers, drug resistance inevitably appeared during the application of Herceptin. In order to fully understand the immune tolerance status of the tumor microenvironment in the population of sensitive and insensitive patients, this study carried out a series of studies through Luminex cytokines assay, clinicopathological analysis, immunofluorescence, and PCR. The results confirmed that in clinical samples sensitive to Herceptin, there were a large number of macrophages, and the protein expression levels and in situ expression of macrophage-related chemokines and inflammatory mediators are significantly higher than drug-resistant tumor samples. Further studies found that T cell function has a low correlation with tumor growth, and there are obvious obstacles in the process of peripheral blood immune cells entering the tumor microenvironment. In summary, this study provided clues for understanding the clinical drug resistance of HER2 monoclonal antibody and the clinical rational use of drugs and combination drugs.

Free text answers to short questions can reflect students' mastery of concepts and their relationships relevant to learning objectives. However, automating the assessment of free text answers has been challenging due to the complexity of natural language. Existing studies often predict the scores of free text answers in a "black box" manner without analyzing their semantic components, which at least partially limit the prediction performance. In this article, we focus on fine-grained semantic facets in free text answers that correspond to knowledge to be mastered. Using a dataset with semantic facet annotation, we first show the correspondence of semantic facet matching states and answer quality, as well as the importance of semantic facets in automatic assessment of answer quality. We then extend the work to a dataset without semantic facet annotation and demonstrate the effectiveness of proposed automated methods in assessing answer quality, including semantic facet extraction, matching state prediction based on a neural framework, and feature engineering with semantic facets. The contribution of this research is twofold: 1) the proposed methods improve state-of-the-art performance of automatic assessment of free text answers and 2) it delves into fine-grained semantic components of free text answers, making it possible to explain the scores and generate detailed feedback.

PurposeThe causal associations between inflammatory factors and atrial fibrillation (AF) remained unclear. We aimed to investigate whether genetically predicted inflammatory proteins are related to the risk of AF, and vice versa.MethodsA bidirectional two-sample Mendelian randomization study was performed. The genetic variation of 91 inflammatory proteins were derived from genome-wide association study (GWAS) data of European ancestry (n = 14,824). Summary statistics for AF were obtained from a published meta-analysis study (n = 1,030,836) and the FinnGen study (n = 261,395).ResultsGenetically predicted fibroblast growth factor 5 (FGF5) was significantly positively associated with risk of AF [[odds ratio (OR): 1.07; 95% CI: 1.04–1.10; P

BackgroundThe safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious.AimsThis study evaluates DAPT’s effectiveness and safety for these patients.MethodsThis review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4.ResultsAnalysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46–0.59, p

Information sources affect people’s tourism, culture, and entertainment buying. It is therefore important to study the apportionment effects by information source type and comprehensively analyze how information sources positively or negatively impact the consumption of tourism, culture, and entertainment. This research analyzed the influence of four information sources on such buying based on data from the China Family Panel Studies (CFPS) from 2014 to 2018. Regression analysis was used to examine the relationships among variables. The findings were that: (1) information sources (Internet, broadcast, print, and word of mouth) had a significant positive impact on tourism, culture, and entertainment buying; (2) the effects of information were significantly different based on age, education level, and place of residence (urban vs. rural); and (3) information source digitalization increased the share of TCE consumption in overall household consumption through improving social interactions and convenience of transactions. The findings contribute to alleviating the information asymmetry in tourism consumption, helping tourism enterprises develop targeted marketing measures, and promoting the improvement of residents’ tourism consumption.

Abstract Background The Malocclusion Impact Scale for Early Childhood (MIS-EC) is a newly developed questionnaire used to measure the parental perceptions of the impact of malocclusion on oral health-related quality of life (OHRQoL) of preschool children aged 3–5 years. This study describes the cross-cultural adaptation and validation of the MIS-EC questionnaire into Chinese version (MIS-EC/C). Methods The MIS-EC/C was developed in accordance with international standards. The scale was then evaluated in a cross-sectional study comprising 210 preschool children aged 3–5 years. The reliability of the MIS-EC/C was tested using internal consistency and test-retest reliability analyses. Cross-cultural validity, discriminant validity and convergent validity were tested. Results The Cronbach’s α value and intraclass correlation coefficient (ICC) value for the MIS-EC/C were 0.943 and 0.873, respectively. Confirmatory factor analysis indicated that the fitting indicators of the two-factor model all reached the standard. The MIS-EC/C can differentiate preschool children with malocclusion from those without malocclusion. In addition, there is a good relationship between the MIS-EC/C and the general oral health question. Conclusion The MIS-EC/C is a reliable and effective assessment tool for assessing the effect of malocclusion on the OHRQoL of preschool children in China.

Abstract Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

ABSTRACT: Objectives: The aim of this study was to characterize the blaKPC-33 in a ST15-K19 ceftazidime-avibactam (CAZ-AVI)-resistant Klebsiella pneumoniae strain after the antibiotic CAZ-AVI was approved for use in Wuxi No. 2 People's Hospital, China. Methods: Antimicrobial susceptibility testing was performed by the microdilution broth method. Whole genome sequencing (WGS) was performed using PacBio II and MiSeq sequencers. High-quality reads were assembled using the SOAPdenovo and GapCloser v1.12, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic characteristics were analysed by using bioinformatics methods. Results: K. pneumoniae strain KPHRJ showed resistance to CAZ-AVI. WGS analysis showed that strain KPHRJ had one 5 536 506 bp chromosome (57.25% G+C content) and one plasmid (133 451 bp, G+C 54.29%). KPHRJ was classified as ST15 and K19 serotype. Resistome analysis showed that KPHRJ carries seven antimicrobial resistance genes (ARGs). WGS analysis and conjugation experiments demonstrated that the blaKPC-33 gene was carried by plasmid pKPHRJ, flanked by two copies of IS26 mobile elements (IS26-ISKpn27-blaKPC-33-ISKpn6-korC-TnAs1-tetR-tetA-Tn3-IS26). Besides these acquired resistance genes, mutations in porin protein-coding genes, such as OmpK36 and OmpK37, which may reduce susceptibility to the CAZ-AVI, were also identified from the genome. Conclusion: Here, we present the WGS of a CAZ-AVI resistant K. pneumoniae isolate, strain KPHRJ, with capsular serotype K19 and belonging to ST15. CAZ-AVI resistance is likely conferred by a KPC-2 variant, blaKPC-33 and mutations in porin-coding genes. We speculate that the approval of the CAZ-AVI in hospital could contribute to the emergence of these genomic features by providing a selective pressure leading to the emergence of CAZ-AVI resistant bacteria.

This is the first report to describe the green fabrication of zinc oxide nanoparticles starting with cera alba (beeswax) extract as an eco-friendly reducing and capping agent. The reaction of zinc nitrate with an aqueous extract of Cera Alba resulted in the formation of zinc oxide nanoparticles (ZnO-W). Treatment of ZnO-W at 550 °C gave pure zinc oxide nanoparticles (ZnO-G). Various techniques, including FT-IR, XRD, TGA, SEM, and HR-TEM, were used to analyze the structures of synthesized nanoparticles. A methylene blue dye solution was used to evaluate the photocatalytic activity. The impact of catalyst dose, reaction time, and pH on photocatalytic degradation under sunlight was studied. At optimal conditions, complete photodegradation of 10 ppm methylene blue occurs in 40 min. The antimicrobial activity of ZnO-G was evaluated against three microbial strains: Bacillus cereus, Escherichia coli, and Candida albicans. The impact of exposing the ZnO-G to various light wavelengths (265 nm, 346 nm, visible light, and sunlight) to inhibit microbial growth was investigated. The best result was obtained when ZnO-G was exposed to 265 nm light. This study's findings support using ZnO-G prepared via cera alba as a powerful photocatalytic and antimicrobial agent.

Abstract Background Primary liver cancer has significant intratumor genetic heterogeneity (IGH), which drives cancer evolution and prevents effective cancer treatment. CRISPR/Cas9-induced mouse liver cancer models can be used to elucidate how IGH is developed. However, as CRISPR/Cas9 could induce chromothripsis and extrachromosomal DNA in cells in addition to targeted mutations, we wondered whether this effect contributes to the development of IGH in CRISPR/Cas9-induced mouse liver cancer. Methods CRISPR/Cas9-based targeted somatic multiplex-mutagenesis was used to target 34 tumor suppressor genes (TSGs) for induction of primary liver tumors in mice. Target site mutations in tumor cells were analyzed and compared between single-cell clones and their subclones, between different time points of cell proliferation, and between parental clones and single-cell clones derived from mouse subcutaneous allografts. Genomic instability and generation of extrachromosomal circular DNA (eccDNA) was explored as a potential mechanism underlying the oscillation of target site mutations in these liver tumor cells. Results After efficiently inducing autochthonous liver tumors in mice within 30–60 days, analyses of CRISPR/Cas9-induced tumors and single-cell clones derived from tumor nodules revealed multiplexed and heterogeneous mutations at target sites. Many target sites frequently displayed more than two types of allelic variations with varying frequencies in single-cell clones, indicating increased copy number of these target sites. The types and frequencies of targeted TSG mutations continued to change at some target sites between single-cell clones and their subclones. Even the proliferation of a subclone in cell culture and in mouse subcutaneous graft altered the types and frequencies of targeted TSG mutations in the absence of continuing CRISPR/Cas9 genome editing, indicating a new source outside primary chromosomes for the development of IGH in these liver tumors. Karyotyping of tumor cells revealed genomic instability in these cells manifested by high levels of micronuclei and chromosomal aberrations including chromosomal fragments and chromosomal breaks. Sequencing analysis further demonstrated the generation of eccDNA harboring targeted TSG mutations in these tumor cells. Conclusions Small eccDNAs carrying TSG mutations may serve as an important source supporting intratumor heterogeneity and tumor evolution in mouse liver cancer induced by multiplexed CRISPR/Cas9.

Individual tree canopy extraction plays an important role in downstream studies such as plant phenotyping, panoptic segmentation and growth monitoring. Canopy volume calculation is an essential part of these studies. However, existing volume calculation methods based on LiDAR or based on UAV-RGB imagery cannot balance accuracy and real-time performance. Thus, we propose a two-step individual tree volumetric modeling method: first, we use RGB remote sensing images to obtain the crown volume information, and then we use spatially aligned point cloud data to obtain the height information to automate the calculation of the crown volume. After introducing the point cloud information, our method outperforms the RGB image-only based method in 62.5% of the volumetric accuracy. The AbsoluteError of tree crown volume is decreased by 8.304. Compared with the traditional 2.5D volume calculation method using cloud point data only, the proposed method is decreased by 93.306. Our method also achieves fast extraction of vegetation over a large area. Moreover, the proposed YOLOTree model is more comprehensive than the existing YOLO series in tree detection, with 0.81% improvement in precision, and ranks second in the whole series for mAP50-95 metrics. We sample and open-source the TreeLD dataset to contribute to research migration.

Canopy volume is a crucial biological parameter for assessing tree growth, accurately estimating forest Above-Ground Biomass (AGB), and evaluating ecosystem stability. Airborne Laser Scanning (ALS) and Terrestrial Laser Scanning (TLS) are advanced precision mapping technologies that capture highly accurate point clouds for forest digitization studies. Despite advances in calculating canopy volume, challenges remain in accurately extracting the canopy and removing gaps. This study proposes a canopy volume extraction method based on an improved PointNeXt model, fusing ALS and TLS point cloud data. In this work, improved PointNeXt is first utilized to extract the canopy, enhancing extraction accuracy and mitigating under-segmentation and over-segmentation issues. To effectively calculate canopy volume, the canopy is divided into multiple levels, each projected into the xOy plane. Then, an improved Mean Shift algorithm, combined with KdTree, is employed to remove gaps and obtain parts of the real canopy. Subsequently, a convex hull algorithm is utilized to calculate the area of each part, and the sum of the areas of all parts multiplied by their heights yields the canopy volume. The proposed method’s performance is tested on a dataset comprising poplar, willow, and cherry trees. As a result, the improved PointNeXt model achieves a mean intersection over union (mIoU) of 98.19% on the test set, outperforming the original PointNeXt by 1%. Regarding canopy volume, the algorithm’s Root Mean Square Error (RMSE) is 0.18 m3, and a high correlation is observed between predicted canopy volumes, with an R-Square (R2) value of 0.92. Therefore, the proposed method effectively and efficiently acquires canopy volume, providing a stable and accurate technical reference for forest biomass statistics.