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Background: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy., Methods: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency., Results: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains., Conclusion: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

FHV-1 is a highly contagious pathogen that significantly threatens feline health and contributes to rising pet healthcare costs. The mechanisms underlying FHV-1 and host interactions remain poorly understood. For the first time, we conducted a systematic analysis of transcriptomic changes in CRFK cells following FHV-1 infection using RNA-seq. The differentially expressed genes (DEGs) displayed significant associations with cellular components, particularly the chromatin structure. Pathway analysis of the DEGs highlighted key host immune responses, including Toll-like receptors (TLRs), IL-17, TNF, MAPK, and Rap1 signaling pathways. By integrating the RNA-seq and RT-qPCR results, we identified CXCL8, CXCL10, MMP1, MMP9, CSF2, CSF3, CCL20, TLR2, TLR3, TLR4, TNF, and FOS as potentially important genes in the host's immune response to FHV-1. These findings provide valuable insights into the mechanisms underlying FHV-1 and host interactions.

Background: Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice., Methods: Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase., Results: The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels., Conclusions: Therefore, CGA has a protective impact on testicular injuries arising from CP in mice., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The incidence and mortality rates of malignant tumors, such as acute leukemia, have risen significantly. Clinically, hospitals rely on cytological examination of peripheral blood and bone marrow smears to diagnose malignant tumors, with accurate blood cell counting being crucial. Existing automated methods face challenges such as low feature expression capability, poor interpretability, and redundant feature extraction when processing highdimensional microimage data. We propose a novel finegrained classification model, SCKansformer, for bone marrow blood cells, which addresses these challenges and enhances classification accuracy and efficiency. The model integrates the Kansformer Encoder, SCConv Encoder, and Global-Local Attention Encoder. The Kansformer Encoder replaces the traditional MLP layer with the KAN, improving nonlinear feature representation and interpretability. The SCConv Encoder, with its Spatial and Channel Reconstruction Units, enhances feature representation and reduces redundancy. The Global-Local Attention Encoder combines Multi-head Self-Attention with a Local Part module to capture both global and local features. We validated our model using the Bone Marrow Blood Cell FineGrained Classification Dataset (BMCD-FGCD), comprising over 10,000 samples and nearly 40 classifications, developed with a partner hospital. Comparative experiments on our private dataset, as well as the publicly available PBC and ALL-IDB datasets, demonstrate that SCKansformer outperforms both typical and advanced microcell classification methods across all datasets.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 10 6 -10 8 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant ( P < 0.01). There was an interaction effect between concentration and time ( P = 0.0448), and there was also an interaction effect between temperature and time ( P < 0.01). There was no interaction effect between concentration and temperature ( P = 0.11) or between concentration, temperature, and time ( P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C., Importance: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control., Competing Interests: The authors declare no conflict of interest.

Multi-informant studies are popular in social and behavioral science. However, their data analyses are challenging because data from different informants carry both shared and unique information and are often incomplete. Using Monte Carlo Simulation, the current study compares three approaches that can be used to analyze incomplete multi-informant data when there is a distinction between reference and nonreference informants. These approaches include a two-method measurement model for planned missing data (2MM-PMD), treating nonreference informants' reports as auxiliary variables with the full-information maximum likelihood method or multiple imputation, and listwise deletion. The result suggests that 2MM-PMD, when correctly specified and data are missing at random, has the best overall performance among the examined approaches regarding point estimates, type I error rates, and statistical power. In addition, it is also more robust to data that are not missing at random., (© 2024. The Psychonomic Society, Inc.)

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NP Ce6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H 2 O 2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NP Ce6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety., Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues., Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D., Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels., Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology., (© 2024 The Authors.)

Saponins are an important class of active components in Chinese herbal medicines (CHMs), which are present in large quantities in Ginseng Radix et Rhizoma , Notoginseng Radix et Rhizoma , Polygonati Rhizoma , etc., and have immune regulation, anti-tumor, anti-inflammatory, anti-cardiovascular disease, and hypoglycemic activities. Storage and processing are essential processes in the production process of CHMs which affect the stability of saponin components and then reduce the medicinal and economic value. Therefore, it is of great importance to investigate the effects of storage and processing conditions on the content of saponin components in CHMs. In this paper, the effects of various storage and processing factors, including temperature, pH, enzymes, meta lions, extraction methods, etc., on the saponin content of CHMs are investigated and the underlying mechanisms for the quantitative changes of saponin are summarized. These findings may provide technical guidance for the production and processing of saponin-rich CHMs.

Background: Lung adenocarcinoma (LUAD) is a common type of malignant tumor with therapeutic challenges. Cancer-associated fibroblasts (CAFs) promote LUAD growth and metastasis, regulate the tumor immune response, and influence tumor treatment responses and drug resistance. However, the molecular mechanisms through which CAFs control LUAD progression are largely unknown. In this study, we aimed to determine the correlations between CAF-related genes and overall survival (OS) in patients with LUAD., Methods: We acquired the gene expression data and clinical information of 522 patients with LUAD patients from The Cancer Genome Atlas (TCGA) and 442 patients with LUAD from the Gene Expression Omnibus (GEO) databases. CAF infiltration levels were assessed using the Microenvironment Cell Population (MCP) counter, the Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. A CAF-related gene network was constructed using the Weighted gene co-expression network analysis (WGCNA). Based on the CAF-related genes, univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to identify prognostic genes. Gene expression levels within the prognostic model were validated using the Cancer Cell Line Encyclopedia (CCLE) databases and Western blotting., Results: Our results demonstrated that high CAF scores were associated with lower survival rates in patients with LUAD. Gene modules that were highly correlated with high CAF scores were closely associated with tissue characteristics and extracellular matrix structures in LUAD. In addition, correlations between CAF scores and responses to immunotherapy and chemotherapy were observed. Finally, we found that SNAI2 expression was higher in lung cancer tissues than in normal tissues., Conclusion: Deepening our understanding of the influence of CAFs on tumor progression and treatment response at the molecular level can aid the development of more effective therapeutic strategies. This study provides important insights into the functional mechanisms of action of CAFs in LUAD and highlights their clinical implications., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

An aerobic copper-catalyzed oxysulfonylation of vinylarenes with sodium sulfinates is described. This protocol features mild reaction conditions, convenient operation, and broad substrate scope with respect to vinylarenes and sodium sulfinates. Notably, the protocol demonstrates excellent tolerance of functional groups such as chloro, bromo, ester, cyano, and nitro groups. Mechanistic investigations indicated that the reaction should undergo radical cascades involving a sulfonyl radical generated from sodium sulfinate with air as the terminal oxidant, addition across alkene to deliver a benzylic radical, and subsequent cross-coupling with air.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Peach brown rot, caused by the pathogen Monilinia fructicola, represents a significant postharvest infectious disease affecting peach fruit. This disease is responsible for a substantial increase in fruit decay rates, leading to significant economic losses, often exceeding 50%. Currently, there is a growing interest in identifying biocontrol agents to mitigate peach brown rot, with a predominant interest in Bacillus species., Results: In this investigation, we isolated 410 isolates of actinomycetes from non-farmland ecosystem soil samples. Subsequently, 27 isolates exhibiting superior inhibitory capabilities were selected. Among these, strain XDS1-5 demonstrated the most robust fungistatic effect against brown rot disease, achieving an 80% inhibition rate in vitro and a 66% inhibition rate in vivo. XDS1-5 was identified as belonging to the Streptomyces virginiae species. Furthermore, a fermentation filtrate of XDS1-5 exhibited the ability to metabolize 34.21% of the tested carbon sources and 7.37% of the tested nitrogen sources. Particularly noteworthy was its capacity to disrupt the cell membrane structure directly, leading to increased cell membrane permeability and cytoplasmic leakage. Additionally, our investigation indicated that indoline, a metabolite produced by XDS1-5, played a pivotal role in inhibiting the growth of M. fructicola., Conclusion: In summary, our study has identified a biocontrol actinomycete, XDS1-5, with the potential to effectively inhibit postharvest brown rot disease in peaches. This finding holds great significance for the biological control of peach brown rot, offering promising prospects for mitigating the economic losses associated with this devastating disease. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses., (© 2024. The Author(s).)

Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO 2 ) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO 2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.

The Bohai Rim Plain is an important grain-producing area in China. The cultivated land resources have great potential for production, but there are many influencing factors. Understanding the spatiotemporal change characteristics and driving factors of the net primary productivity （NPP） of cultivated land vegetation in this region is of great significance to improve the regional cultivated land production conditions, excavate and enhance the production capacity of cultivated land, and ensure national food security. In this study, Theil-Sen Median trend analysis, Mann-Kendall significance test, Hurst index, and other methods were used to explore the spatiotemporal change characteristics, stability, and sustainability of regional cultivated land NPP. The influence of driving factors on the spatial heterogeneity of cultivated land NPP was analyzed by using optical parameters-based geographical detectors. The results showed that： ① From 2001 to 2019, due to the expansion of construction land during industrialization and urbanization, the cumulative decrease in the area of cultivated land in the Shandong area around the Bohai Sea was 2 004.51 km 2 . ② During the selected research period, the interannual variation of average cultivated land NPP showed a fluctuating and increasing trend. In terms of spatial distribution, the NPP of cultivated land was bounded by the Dongying District, with the spatial heterogeneity in the north being significantly lower than that in the south. ③ The area with increasing NPP of cultivated land accounted for 88.06% of the total area of cultivated land, mainly with low and medium fluctuations. The NPP of cultivated land will maintain an overall sustained trend of increase across the region in the future. ④ The average annual relative humidity study area had the strongest explanatory power for the spatial variability of NPP in cropland, with a q -value of 0.26, followed by surface soil salinity and subsoil salinity, with q -values greater than 0.2. The interactions between the different drivers all showed either nonlinear enhancement or bifactorial enhancement. The results of this study will help to reveal the characteristics of the changes in cultivated land production capacity and its driving forces in the Bohai Sea region and also provide a theoretical basis for the ecological protection and sustainable development of the region.

Background: The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery., Purpose: Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon-based identification methods., Materials and Methods: Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full-length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the model's performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons., Results: Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real-time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001)., Conclusion: The AI-driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes., (© 2024 Wiley Periodicals LLC.)

A nickel-catalyzed direct sulfonylation of alkenes with sulfonyl chlorides has been developed using 1,10-phenanthroline-5,6-dione as the ligand. Unactivated alkenes and styrenes including 1,1-, 1,2-disubstituted alkenes can be subjected to the protocol, and a wide range of vinyl sulfones was obtained in high to excellent yields with good functional group compatibility. Notably, the process did not allow the desulfonylation of sulfonyl chloride or chlorosulfonylation of alkenes. Radical-trapping experiment supported that a sulfonyl free-radical was likely produced and triggered subsequent transformation in the process.

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection-those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many high-priority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Davis, Jia, Wright, Islam, Bean, Layton, Williams and Lynch.)

Under transient greenhouse warming, El Niño-Southern Oscillation (ENSO) is projected to increase pre-2100, accompanied by an easier establishment of atmospheric convection in the equatorial eastern Pacific, where sea surface temperature (SST) warms faster than surrounding regions. After 2100, how ENSO variability may change remains unknown. Here we find that under a high emission scenario, ENSO variability post-2100 reverses from the initial increase to an amplitude far smaller than that of the 20 th century. The fast eastern warming persists and shrinks the equatorial Pacific non-convective area, such that establishing convection in the non-convective area, as during an El Niño, requires smaller convective anomaly, inducing weaker wind anomalies leading to reduced ENSO SST variability. The nonlinear ENSO response is thus a symptom of the persistent El Niño-like warming pattern. Therefore, the oscillatory ENSO impact could be replaced by that from the permanent El Niño-like mean condition with cumulative influences on affected regions., (© 2024. The Author(s).)

Rationale: Nontuberculous mycobacteria (NTM) has been reported to be transmitted between people with cystic fibrosis (CF) attending CF centres. A suspected Mycobacterium abscessus outbreak was investigated at the University of Texas Southwestern (UTSW) Adult CF Program using a combination of pathogen genomic sequencing and epidemiologic methods. The objectives of the present study were to apply the Healthcare-Associated Links in Transmission of NTM (HALT NTM) study to investigate the occurrence of potential healthcare-associated transmission and/or acquisition of NTM among people with CF infected with genetically similar NTM isolates., Methods: Whole-genome sequencing of respiratory M. abscessus isolates from 50 people with CF receiving care at UTSW was performed to identify genetically similar isolates. Epidemiologic investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping were studied., Measurements and Main Results: Whole-genome sequencing analysis demonstrated seven clusters of genetically similar M. abscessus (four ssp . abscessus and three ssp. massiliense ). Epidemiologic investigation revealed potential opportunities for healthcare-associated transmission within three of these clusters. Healthcare environmental sampling did not recover M. abscessus , but did recover four human disease-causing species of NTM. No subjects having clustered infections lived in the same home residence watershed. Some subjects were infected with more than one M. abscessus genotype, both within and outside of the dominant circulating clones., Conclusions: Healthcare-associated person-to-person transmission of M. abscessus appears to be rare at this centre. However, polyclonal infections of M. abscessus species and subspecies, not originating from the endemic hospital environment, suggest multiple shared modes of acquisition outside the healthcare setting., Competing Interests: Conflict of interest: J.E. Gross reports support for the present manuscript from the Cystic Fibrosis (CF) Foundation and grants or contracts from CF Foundation outside the submitted work; and is a board member of the Rocky Mountain Chapter of the Cystic Fibrosis Foundation and Chair of the American Board of Pediatrics Pulmonology Subboard, disclosures made outside the submitted work. Conflict of interest: J.D. Finklea reports support for the present manuscript from a CF Foundation QI improvement grant, CF Foundation Success with Therapies Research Consortium. Conflict of interest: C.K. Vang reports support for the present manuscript from the CF Foundation. Conflict of interest: J.R. Honda reports support for the present manuscript from the Padosi Foundation and the University of Texas Health Science Center at Tyler; grants or contracts from the National Science Foundation, National Institutes of Health, CF Foundation and the John Chapman Endowed Professorship in Microbiology, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from the North American CF Foundation, Yale University, National Jewish Health, NTM Research Consortium and Albert Einstein College of Medicine, outside the submitted work; support for attending meetings and/or travel from the Padosi Foundation, National Science Foundation, National Jewish Health, NIH AGOLD-PRIDE, Albert Einstein College of Medicine, Sam Houston State University, American Thoracic Society, Texas Tech University, Colorado State University, NTM Research Consortium and North American CF Foundation, outside the submitted work; a leadership or fiduciary role for the American Thoracic Society, outside the submitted work; and receipt of equipment, materials, drugs, medical writing, gifts or other services from the University of Texas Health Science Center at Tyler, outside the submitted work. Conflict of interest: M. Strand reports support for the present manuscript from Effort from CF Foundation grant “Prospective Healthcare-Associated Transmission of Nontuberculous Mycobacteria”. Conflict of interest: C.L. Daley reports support for the present manuscript from CF Foundation; grants or contracts from AN2, Bugworks, Insmed, Juvabis and Paratek, outside the submitted work; consulting fees from Genentech and Pfizer, outside the submitted work; and participation on a data safety monitoring or advisory board for AN2, AstraZeneca, Hyfe, Insmed, MannKind, Matinas Biopharma, Nob Hill, Paratek, Spero and Zambon, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Quantitative analysis of the spatial non-stationary characteristics of soil salinization influencing factors and the prediction of its spatial distribution are of great significance for the rational use of coastal saline soil resources and the formulation of local prevention and control measures. In this study, the Hekou District of Dongying City, Shandong Province, was used as the study area, and the descriptive statistics of soil salinization status were conducted using classical statistical methods. Spatial autocorrelation theory was used to explore the characteristics of global and local spatial structure of soil salinization in the study area. Influential factors related to soil salinity were selected, and multivariate linear regression （MLR）, geographically weighted regression （GWR）, and multi-scale geographically weighted regression （MGWR） methods were used to model and predict the spatial distribution of soil salinity in the study area and to analyze the spatial heterogeneity of the effects of different influencing factors on soil salinity. The results showed that： ① The mean value of soil salinity in the study area was 5.84 g·kg -1 , indicating severe salinization, with a global Moran's I index of 0.19 （ P <0.00） and obvious spatial aggregation characteristics. ② Among the three models, the MGWR model had the highest modeling accuracy. Compared with that of the MLR model, the R adj 2 of GWR and MGWR improved by 0.05 and 0.07, respectively, and the RSS decreased by 210.13 and 179.95, respectively. ③ The results of MGWR regression showed that the spatial distribution of soil salinity appeared to be mainly affected by the middle soil salinity, soil clay content, and vegetation cover from the mean values of standardized regression coefficients of different influencing factors. Different influencing factors had significant spatial non-stationary characteristics on soil salinization. ④ The results of the spatial distribution prediction of soil salinity in MGWR showed that the areas of high soil salinity （≥6 g·kg -1 ） were mainly distributed in the northern part of the study area, with an overall spatial trend of decreasing from the coast to the interior. The results of the study can be used as a reference for the analysis and predictive mapping of factors affecting soil salinization in the county and on a larger scale using MGWR.

Peach brown rot, attributed to Monilinia fructicola, presents a significant threat to postharvest peach cultivation, causing losses of up to 80%. With an increasing number of countries, spearheaded by the European Union, imposing bans on chemical agents in fruit production, there is a growing interest in mining highly active antibacterial compounds from biological control strains for postharvest disease management. In this study, we highlight the unique ability of Streptomyces lincolnensis strain JCP1-7 to inhibit M. fructicola sporulation, despite its limited antimicrobial efficacy. Through GC-MS analysis, eucalyptol was identified as the key compound. Fumigation of diseased fruits with eucalyptol at a concentration of 0.0335 μg cm -3 demonstrated an in vivo inhibition rate against M. fructicola of 93.13%, completely suppressing spore formation. Transcriptome analysis revealed the impact of eucalyptol on multiple pathogenesis-related pathways, particularly through the inhibition of catalase 2 (Cat2) expression. Experiments with a MfCat2 knockout strain (ΔMfCat2) showed reduced pathogenicity and sensitivity to JCP1-7 and eucalyptol, suggesting MfCat2 as a potential target of JCP1-7 and eucalyptol against M. fructicola. Our findings elucidate that eucalyptol produced by S. lincolnensis JCP1-7 inhibits M. fructicola sporulation by regulating MfCat2, thereby effectively reducing postharvest peach brown rot occurrence. The use of fumigation of eucalyptol offers insights into peach brown rot management on a large scale, thus making a significant contribution to agricultural research., (© 2024 The Author(s). Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus.

Background: Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis., Method: All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots., Result: The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup., Conclusion: The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies., (© 2024. The Author(s).)

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 μmol) and catechol (100 μmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery., (© 2024. The Author(s).)

We identified 23 cases of Mycobacterium immunogenum respiratory acquisition linked to a colonized plumbing system at a new hospital addition. We conducted a genomic and epidemiologic investigation to assess for clonal acquisition of M. immunogenum from hospital water sources and improve understanding of genetic distances between M. immunogenum isolates. We performed whole-genome sequencing on 28 M . immunogenum isolates obtained from August 2013 to July 2021 from patients and water sources on four intensive care and intermediate units at an academic hospital. Study hospital isolates were recovered from 23 patients who experienced de novo respiratory isolation of M. immunogenum and from biofilms obtained from five tap water outlets. We also analyzed 10 M . immunogenum genomes from previously sequenced clinical ( n = 7) and environmental ( n = 3) external control isolates. The 38-isolate cohort clustered into three clades with pairwise single-nucleotide polymorphism (SNP) distances ranging from 0 to 106,697 SNPs. We identified two clusters of study hospital isolates in Clade 1 and one cluster in Clade 2 for which clinical and environmental isolates differed by fewer than 10 SNPs and had less than 0.5% accessory genome variation. A less restrictive combined threshold of 40 SNPs and 5% accessory genes reliably captured additional isolates that met clinical criteria for hospital acquisition, but 12 (4%) of 310 epidemiologically unrelated isolate pairs also met this threshold. Core and accessory genome analyses confirmed respiratory acquisition of multiple clones of M. immunogenum from hospital water sources to patients. When combined with epidemiologic investigation, genomic thresholds accurately distinguished hospital acquisition., Competing Interests: A.W.B. reports funding from Insmed for clinical trials (payments to the institution) and the Centers for Disease Control and Prevention (payments to the institution), outside of the submitted work. J.E.S. reports funding from AN2 Pharmaceuticals for clinical trials (payments to the institution), UpToDate, and the Academy for Continued Healthcare Learning, outside of the submitted work. A.M.G. reports participation on the Society for Healthcare Epidemiology of America Webinar Program Committee, outside of the submitted work. B.G.W. reports funding from the Centers for Disease Control and Prevention (contract paid to the institution) and participation on the Society for Healthcare Epidemiology of America Guidelines Committee, outside of the submitted work. M.J.L. reports equity in Resonantia Diagnostics and a pending patent pertaining to biofilm, outside of the submitted work. R.M.D. reports funding from the Cystic Fibrosis Foundation and the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants paid to the institution), outside of the submitted work. D.J.A. reports funding from the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention (grants paid to the institution), as well as UpToDate and Infection Control Education for Major Sports, outside of the submitted work. All other authors have no potential conflicts of interest to declare.

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of menstrual disorders in women of childbearing age. It has been found that branched-chain amino acids (BCAAs), a class of essential amino acids that cannot be synthesized by the human body, play a significant role in the metabolic changes of PCOS, which may be involved in the pathogenesis of PCOS., Objective: The purpose of this review is to summarize the relevance between BCAAs and metabolic abnormalities in PCOS and to explore their possible mechanisms., Evidence Acquisition: The evidence is mainly obtained by reviewing the literature on PubMed related to PCOS, BCAAs, and related metabolic abnormalities and conducting summary analysis., Results: The metabolism of BCAAs can affect the homeostasis of glucose metabolism, possibly by disrupting the balance of gut microbiota, activating mTORC1 targets, producing mitochondrial toxic metabolites, and increasing the expression of proinflammatory genes. The correlation between obesity and BCAAs in PCOS patients may be related to the gene expression of BCAA metabolism-related enzymes in adipose tissue. The association between BCAA metabolic changes and nonalcoholic fatty liver disease in PCOS patients has not been fully clarified, which may be related to the lipid accumulation caused by BCAAs. At present, it is believed that hyperandrogenism in patients with PCOS is not related to BCAAs. However, through the study of changes in BCAA metabolism in prostate cancer caused by hyperandrogenism, we speculate that the relationship between BCAAs and hyperandrogenism may be mediated by mTORC1 and amino acid transporters., Conclusions and Relevance: Review of prior articles reveals that BCAAs may be related to insulin resistance, obesity, nonalcoholic fatty liver, and hyperandrogenism in PCOS patients, and its mechanisms are complex, diverse, and interrelated. This review also discussed the mechanism of BCAAs and these metabolic disorders in non-PCOS patients, which may provide some help for future research.

In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum, assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading., Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI)., Results: Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17 + GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils., Conclusions: Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17 + GBC cells in GBC-LI., (© 2024. The Author(s).)

Over the past decade, significant progress has been made in the direct C-H acylation of naphthalenes, occurring at the α or β-positions to yield valuable ketones through Friedel-Crafts acylation or transition-metal-catalysed carbonylative coupling reactions. Nevertheless, highly regioselective acylation of naphthalenes remains a formidable challenge. Herein, we developed a nickel-catalysed reductive ring-opening reaction of 7-oxabenzonorbornadienes with acyl chlorides as the electrophilic coupling partner, providing a new method for the exclusive preparation of β-acyl naphthalenes.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE., Competing Interests: The authors declare no conflict of interest.

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro , it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To investigate the efficacy of graded motor imagery therapy (GMI) and repetitive transcranial magnetic stimulation (rTMS) on upper extremity function alone and in combination in patients with stroke., Design: This was a prospective randomized controlled trial., Setting: A rehabilitation hospital., Participants: Participants (N=56) were randomized into GMI (n=19), rTMS (n=18), or combined groups (n=19)., Interventions: There were 2 interventions: (1) 20 minutes of 1 Hz rTMS. (2) 30 minutes of GMI. In addition to this, all participants receive conventional rehabilitation including 120 minutes of physical therapy and occupational therapy daily. All treatments were administered once a day, 5 days a week, for 4 weeks. The Fugl-Meyer assessment of upper extremity (FMA-UE), Action Research Arm Test (ARAT), modified Barthel Index (MBI), motor activity log (MAL), and motor evoked potential (MEP) were assessed in a blinded manner at baseline and 4 weeks after treatment, respectively., Main Outcome Measures: The primary endpoint was the improvement from baseline in FMA-UE for stroke patients at 4 weeks., Results: After 4 weeks of treatment, the FMA-UE scores in the GMI, rTMS, and combined groups were higher than those at baseline assessment, with statistically significant differences among the 3 groups (P=.009). The efficacy of the combined group was significantly better than that of the GMI and rTMS groups (P=.015, P=.043, respectively). In the motor activity log-amount of use (MAL-AOU) score, the efficacy of the combined group was better than that of the rTMS group (P=.035)., Conclusions: Both GMI and rTMS were effective in improving upper extremity function in patients with stroke, but the combination of the 2 techniques was more effective. However, GMI was better than rTMS in improving the interest of stroke patients in active training., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies., Methods: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis., Results: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility., Conclusion: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information., (© 2024 Wiley Periodicals LLC.)

Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Bacterial diseases could severely harm agricultural production. To develop new antibacterial agents, the secondary metabolites of a deep-sea-derived fungus Simplicillium obclavatum EIODSF 020 with antibacterial activities against plant and fish pathogens were investigated by a bioassay-guided approach, which led to the isolation of 11 new peptaibiotics, simplicpeptaibs A-K ( 1 - 11 ). They contain 16-19 residues, including β-alanine, tyrosine, or tyrosine O -sulfate, that were rarely present in peptaibiotics. Their structures were elucidated by spectroscopic analyses (NMR, HRMS, HRMS 2 , and ECD) and Marfey's method. The primary and secondary structures of novel sulfated peptaibiotic 9 were reconfirmed by single-crystal X-ray diffraction analysis. Genome sequencing of S. obclavatum EIODSF 020 allowed the detection of a gene cluster encoding two individual NRPSs (totally containing 19 modules) that was closely related to simplicpeptaib biosynthesis. Antibacterial investigations of 1 - 11 together with the previously isolated linear and cyclic peptides from this strain suggested the antibacterial property of this fungus was attributed to the peptaibiotics and cyclic lipopeptides. Among them, compounds 4 , 6 , 7 , and 9 showed significant activity against the tobacco pathogen Ralstonia solanacearum or tilapia pathogens Streptococcus iniae and Streptococcus agalactiae . The antibacterial activity of 6 against R. solanacearum could be enhanced by the addition of 1% NaCl. The structure-bioactivity relationship of simplicpeptaibs was discussed.

Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO - ) species and limit the therapeutic effect of NO. Hence, we design a ROS-responsive NO nanomedicine (t-PBA&NO NP) with ROS scavenging ability to solve the dilemma of NO-based therapy. t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate (ECA) to the injury sites via collagen IV homing peptide. The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging, endoplasmic reticulum and mitochondrial regulation. It subsequently maximizes vascular modulation effects of NO, without production of harmful compounds, reactive nitrogen species (RNS). Therefore, it significantly increases competitiveness of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) both in vitro and in vivo. The strategy proved effective in inducing faster re-endothelialization, inhibiting neointimal formation and restoring vascular homeostasis. The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In structural equation modeling, when multiple imputation is used for handling missing data, model fit evaluation involves pooling likelihood-ratio test statistics across imputations. Under the normality assumption, the two most popular pooling approaches were proposed by Li et al. (Statistica Sinica, 1(1), 65-92, 1991) and Meng and Rubin (Biometrika, 79(1), 103-111, 1992). When the assumption of normality is violated, it is not clear how well these pooling approaches work with the test statistics generated from various robust estimators and multiple imputation methods. Jorgensen and colleagues (2021) implemented these pooling approaches in their R package semTools; however, no systematical evaluation has been conducted. In this simulation study, we examine the performance of these approaches in working with different imputation methods and robust estimators under nonnormality. We found that the naïve pooling approach based on Meng and Rubin (Biometrika, 79(1), 103-111, 1992; D 3SN ) worked the best when combining with the normal-theory-based imputation and either MLM or MLMV estimator., (© 2023. The Psychonomic Society, Inc.)

Herein we reported a directing-group assisted strategy for nickel-catalysed reductive defluorinative sulfenylation of trifluoropropionic acid derivatives with disulfides in the presence of Zn, involving triple C-F bond cleavage. This process yielded a diverse array of carbonyl-sulfide di-substituted alkenes in moderate to good yields with good functional group tolerance. Specifically, the reactions exhibited high E -selectivity with E / Z ratio up to >99 : 1.

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery., Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics., Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased., Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Yu, Ao, Wang, Guo, Li, Huang, Zhou, Yan, Zhang, Wang, Cai, Lin and Zhao.)

This article reviewed the relationship between the autonomic nervous system and the development of polycystic ovary syndrome (PCOS). PCOS is the most common reproductive endocrine disorder among women of reproductive age. Its primary characteristics include persistent anovulation, hyperandrogenism, and polycystic ovarian morphology, often accompanied by disturbances in glucose and lipid metabolism. The body's functions are regulated by the autonomic nervous system, which consists mainly of the sympathetic and parasympathetic nervous systems. The autonomic nervous system helps maintain homeostasis in the body. Research indicates that ovarian function in mammals is under autonomic neural control. The ovaries receive central nervous system information through the ovarian plexus nerves and the superior ovarian nerves. Neurotransmitters mediate neural function, with acetylcholine and norepinephrine being the predominant autonomic neurotransmitters. They influence the secretion of ovarian steroids and follicular development. In animal experiments, estrogen, androgens, and stress-induced rat models have been used to explore the relationship between PCOS and the autonomic nervous system. Results have shown that the activation of the autonomic nervous system contributes to the development of PCOS in rat. In clinical practice, assessments of autonomic nervous system function in PCOS patients have been gradually employed. These assessments include heart rate variability testing, measurement of muscle sympathetic nerve activity, skin sympathetic response testing, and post-exercise heart rate recovery evaluation. PCOS patients exhibit autonomic nervous system dysfunction, characterized by increased sympathetic nervous system activity and decreased vagal nerve activity. Abnormal metabolic indicators in PCOS women can also impact autonomic nervous system activity. Clinical studies have shown that various effective methods for managing PCOS regulate patients' autonomic nervous system activity during the treatment process. This suggests that improving autonomic nervous system activity may be an effective approach in treating PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Chen, Zheng, Jia, Liao, Ren, Liu and Liu.)

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Postpartum dysfunctions and complications can occur in women. However, functional assessment should be conducted to make treatment plans before any intervention is implemented. In this context, the International Classification of Functioning, Disability and Health (ICF) may be a useful tool for women postpartum to document functional data and set rehabilitation goals. The purpose of this study was to determine the corresponding domains that should be considered in the evaluation of women's postpartum functioning based on the International Classification of Functioning, Disability and Health (ICF) model using the Delphi method., Methods: Fifteen domestic experts were invited to conduct two rounds of expert consensus survey on the ICF-based postpartum functional assessment category pool obtained through literature retrieval, clinical investigation, and reference to relevant literature. The sample was medical staff with professional knowledge of women's health. The opinions of experts were summarized, and the positive coefficient, authority coefficient and coordination degree of experts were calculated., Results: A total of 15 domestic experts participated in this expert consensus. Through two rounds of a questionnaire survey, 69 items were finally selected to form the ICF-based postpartum functional assessment tool for women. The items included 32 items of body function, 12 items of body structure, 17 items of activity and participation, and 8 items of environmental factors. In addition, we identified 8 items of personal factors. The expert positive coefficients of the two rounds of expert consensus were both 100%, the authority coefficient was 0.789, and the coefficient of variation was between 0.09 to 0.31., Conclusion: A postpartum functional assessment tool for women based on the ICF model was constructed based on the Delphi method, which can provide more comprehensive health management and life intervention for postpartum women., Trial Registration: The Registration number of the Chinese Clinical Trial Registry is ChiCTR2200066163, 25/11/2022., (© 2024. The Author(s).)

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract- loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nanoparticles of biological origin exhibit many unique properties in biological applications due to their exquisite structure, specific composition, and natural biological functionality. In this study, we obtained lysosomes from three distinct cell types (one normal cell and two activated immune cells) and demonstrated their potential as natural therapeutic nanoparticles for tumor therapy. In vitro experiments revealed that these lysosomes maintained their structural integrity, were well-distributed, and exhibited significant biological activity, which effectively induced cancer cell death by generating ROS and disrupting biological substrates. Additionally, in vivo investigations showed that these lysosomes could accumulate in tumor tissues after intravenous administration and exhibited exceptional therapeutic effects through the destruction of tumor blood vessels and the degradation of immunosuppressive proteins, with complete tumor disappearance in a single treatment. This research on the utilization of bioactive lysosomes for tumor treatment provides valuable insights into drug development and tumor treatment, particularly when conventional approaches have proven ineffective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The recovery of upper limb function is crucial to the daily life activities of stroke patients. Brain-computer interface technology may have potential benefits in treating upper limb dysfunction., Objective: To systematically evaluate the efficacy of brain-computer interfaces (BCI) in the rehabilitation of upper limb motor function in stroke patients., Methods: Six databases up to July 2023 were reviewed according to the PRSIMA guidelines. Randomized controlled trials of BCI-based upper limb functional rehabilitation for stroke patients were selected for meta-analysis by pooling standardized mean difference (SMD) to summarize the evidence. The Cochrane risk of bias tool was used to assess the methodological quality of the included studies., Results: Twenty-five studies were included. The studies showed that BCI had a small effect on the improvement of upper limb function after the intervention. In terms of total duration of training, < 12 hours of training may result in better rehabilitation, but training duration greater than 12 hours suggests a non significant therapeutic effect of BCI training., Conclusion: This meta-analysis suggests that BCI has a slight efficacy in improving upper limb function and has favorable long-term outcomes. In terms of total duration of training, < 12 hours of training may lead to better rehabilitation.