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High‐order interactions associated with non‐small cell lung cancer (NSCLC) survival may elucidate underlying molecular mechanisms and identify potential therapeutic targets. Our previous work has identified a three‐way interaction among pack‐year of smoking (the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked) and two DNA methylation probes (cg05293407TRIM27 and cg00060500KIAA0226). However, whether a four‐way interaction exists remains unclear. Therefore, we adopted a two‐phase design to identify the four‐way gene–smoking interactions by a hill‐climbing strategy on the basis of the previously detected three‐way interaction. One CpG probe, cg16658473SHISA9, was identified with FDR‐q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase. Meanwhile, the four‐way interaction improved the discrimination ability for the prognostic prediction model, as indicated by the area under the receiver operating characteristic curve (AUC) for both 3‐ and 5‐year survival. In summary, we identified a four‐way interaction associated with NSCLC survival among pack‐year of smoking, cg05293407TRIM27, cg00060500KIAA0226 and g16658473SHISA9, providing novel insights into the complex mechanisms underlying NSCLC progression.

Abstract Lin28 is a key regulator of cancer stem cell gene network that promotes therapy-resistant tumor progression in various tumors. However, no Lin28 inhibitor has been approved to treat cancer patients, urging exploration of novel compounds as candidates to be tested for clinical trials. In this contribution, we applied computer-aided drug design (CADD) in combination with quantitative biochemical and biological assays. These efforts led to the discovery of Ln268 as a drug candidate that can block Lin28 from binding to its RNA substrates and inhibit Lin28 activities. Ln268 suppressed Lin28-mediated cancer cell proliferation and spheroid growth. Results from nuclear magnetic resonance spectroscopy confirmed that Ln268 perturbs the conformation of the zinc knuckle domain of Lin28, validating the rational drug design by CADD. The inhibitory effects of Ln268 are dependent on Lin28 protein expression in cancer cells, highlighting limited off-target effects of Ln268. Moreover, Ln268 synergizes with several chemotherapy drugs to suppress tumor cell growth. In summary, Ln268 is a promising candidate for further development to target Lin28 as a cancer therapy.

Background: The emergence and transmission of the multidrug resistance gene cfr have raised public health concerns worldwide. Objectives: Multidrug-resistant Staphylococcus equorum isolates can pose a threat to public health. In this study, we have characterised the whole-genome of one Staphylococcus equorum isolate harbouring two distinct cfr-carrying plasmids. Methods: Antimicrobial susceptibility testing was performed by broth microdilution. Genomic DNA was sequenced using both the Illumina HiSeq X Ten and Nanopore MinION platforms. De novo hybrid assembly was performed by Unicycler. Genomic data were assessed by in silico prediction and bioinformatic tools. Results: Staphylococcus equorum isolate SN42 exhibited resistance or high MICs to linezolid, erythromycin, tetracycline, oxacillin, clindamycin, virginiamycin, tiamulin, chloramphenicol and florfenicol. It carried two cfr-harbouring plasmids: the RepA N-family plasmid pSN42–51 K and the Inc18-family plasmid pSN42–50 K. These two plasmids exhibited low structural similarities to the so far reported cfr-carrying plasmids. Both plasmids harboured an arsenic resistance operon, copper and cadmium resistance genes as well as the lincosamide-pleuromutilin-streptogramin A resistance gene lsa(B). In addition, plasmid pSN42–51 K carried two erm(B) genes for macrolide-lincosamide-streptogramin B resistance, the streptomycin resistance gene ant(6)-Ia as well as mercury resistance genes while pSN42–50 K was associated with the heavy metal translocating P-type ATPase gene hmtp. The co-carriage and co-existence of these antimicrobial resistance and heavy metal resistance genes increases the likelihood of co-selection of the cfr-carrying plasmids. Conclusion: This is the first report of S. equorum carrying two distinct cfr-carrying plasmids, underscoring the need for ongoing surveillance to address the potential dissemination of multi-drug resistance in bacteria from food-producing animals to ensure food safety and public health.

Abstract Small molecular RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), participate in the regulation of gene expression. As powerful regulators, miRNAs, take part in posttranscriptional regulation of gene expression and play important roles in the diagnosis and treatment of cancer. Meanwhile, siRNA can induce sequence-specific gene silencing, thus being able to inhibit tumorigenesis by suppressing the expression of their targeted proto-oncogenes. Small RNAs (including naked miRNAs and siRNAs) are easily degraded by circulating RNAase, which can be retarded through the package of nanoparticles. Therefore, nanoparticles help tumor therapy by regulating targeted genes of small RNAs. Here, we reviewed the effects of small RNAs on gene expression; the advantages, disadvantages, and targeted modification of nanoparticles as carriers transporting small RNAs; and the application of nanocarriers delivering small RNA for cancer-targeted therapy.

BackgroundNeuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive subtype of cervical carcinomas with poor prognosis. NECC tends to occur in young age which could severely impair mental and physical health of young patients. Therefore, this study aims to develop an individualized prognostic nomogram for young NECC patients.Methods360 young (≤45 years old) NECC patients were retrospectively selected from the Surveillance, Epidemiology and End Results (SEER) database and were randomly located to a training cohort and an internal validation cohort in a ratio of 7:3. Data from Fujian Cancer Hospital was used as an external validation cohort. Independent prognostic factors were identified by univariate and multivariate Cox regression analysis, and a prognostic nomogram for young NECC was developed. The predictive accuracy and clinical utility of the nomogram were assessed by area under the time-dependent receiver operating characteristic (timeROC) curve (AUC), the concordance index (C-index), calibration plots, and decision curve analysis (DCA). Finally, a simplified scoring system for clinical use was constructed by dividing patients into high-risk and low-risk groups.ResultsPathological type, FIGO stage, and surgery were independent risk factors by univariate and multivariate analysis (P < 0.05). The prognostic nomogram consisting of the above three independent risk factors had high accuracy. The AUC values of 5-year overall survival (OS) in the training, internal validation, and external validation cohorts were 0.805, 0.798 and 0.872, respectively. The prognostic nomogram also presented with good C-index and calibration plots. The DCA curve further confirmed that the nomogram had a high clinical net benefit. According to the median prognostic index (median PI=18.6), all patients were categorized into high-risk group and low-risk group. The 5-year OS of the high-risk NECC group was significantly worse than that of the low-risk group among three cohorts (P

Background: In recent years, the combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) has emerged as the standard first-line treatment for hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer (MBC) patients. However, the comparison between the efficacy of CDK4/6i has been poorly explored before. Moreover, it remains unclear about the optimal choice of CDK4/6i in the first-line treatment for HR+/HER2− MBC patients in Asian, especially Chinese populations. Objectives: Our study aims to compare the efficacy of three CDK4/6i widely used in the Chinese population (palbociclib, abemaciclib, and dalpiciclib) in the real world. Design: From 2020 to 2023, the medical records of patients diagnosed with HR+/HER2− MBC were retrospectively assessed in seven institutions in China. Patients who received first-line palbociclib, abemaciclib, or dalpiciclib plus ET were included. Methods: Demographic and clinical data were retrospectively collected and analyzed. Real-world progression-free survival (rwPFS), overall survival (OS), and objective response rate were used to analyze the clinical outcome. Results: In total, 209 HR+/HER2− MBC patients were eligible for this study. Eighty-eight (42.1%), 79 (37.8%), and 42 (20.1%) patients were administered first-line palbociclib, abemaciclib, or dalpiciclib plus ET. The overall median rwPFS was 19 months, with no significant difference between these three CDK4/6i ( p = 0.84). The results were similar even after propensity score matching. The median OS was not reached. Cox univariate and multivariate regression analysis identified that higher KI67 index, liver metastasis, and primary endocrine resistance were independent risk factors for rwPFS in patients with initial CDK4/6i plus ET. Conclusion: This study presents a comparison of the real-world efficacy between three CDK4/6i widely used in the Chinese population. Palbociclib, abemaciclib, and dalpiciclib demonstrated comparable efficacy in Chinese patients with advanced HR+/HER2− MBC. Trial registration: ClinicalTrials.gov identifier: NCT06344780.

The quality issues of ultra-high-temperature (UHT) milk, such as protein hydrolysis and aging gels throughout shelf life, are caused by proteases from psychrophilic bacteria. However, existing enzyme activity detection techniques have low sensitivity and cannot accomplish the detection of product deterioration caused by low enzyme activity. In this study, an attempt was made to analyze the relationship between enzymatically cleaved peptides and product quality using peptidomics techniques. The impact of psychrophilic bacteria proteases on the quality of UHT milk was investigated based on peptidomics by exogenously adding proteases. The results indicated that the protease activity and protein hydrolysis increased significantly in UHT milk over the storage period. Through peptidomic analysis, 2479 peptides were identified, in which 32 proteins linked to the identified peptides. 17 potential marker peptides, including αS1-casein143–156, β-lactoglobulin99–108, and β-casein39–66, were screened. The correlation of all identified peptides with protease activity and protein hydrolysis was explored by the weighted gene co-expression network analysis (WGCNA) method. The peptidomics technology helps to study the release or degradation of peptides in UHT milk during storage, which can be applied to monitor the shelf life of UHT milk and predict spoilage.

Abstract Background CDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor‐positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes. Methods Patients with HR+ MBC who received CDK4/6i‐based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression‐free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0). Results This study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4–15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki‐67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C‐index of 0.714 (95% confidence interval: 0.640–0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions. Conclusions This real‐world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

Abstract Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Abstract Aims This investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022. Methods Data from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment. Results First-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively. Conclusions Compared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.

Abstract IncX3 plasmids carrying the New Delhi metallo-β-lactamase-encoding gene, bla NDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying bla NDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying bla NDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary β-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the bla NDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of bla NDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of bla NDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds.

Astrocytes derive from different lineages and play a critical role in neuropathic pain after spinal cord injury (SCI). Whether selectively eliminating these main origins of astrocytes in lumbar enlargement could attenuate SCI-induced neuropathic pain remains unclear. Through transgenic mice injected with an adeno-associated virus vector and diphtheria toxin, astrocytes in lumbar enlargement were lineage traced, targeted, and selectively eliminated. Pain-related behaviors were measured with an electronic von Frey apparatus and a cold/hot plate after SCI. RNA sequencing, bioinformatics analysis, molecular experiment, and immunohistochemistry were used to explore the potential mechanisms after astrocyte elimination. Lineage tracing revealed that the resident astrocytes but not ependymal cells were the main origins of astrocytes-induced neuropathic pain. SCI-induced mice to obtain significant pain symptoms and astrocyte activation in lumbar enlargement. Selective resident astrocyte elimination in lumbar enlargement could attenuate neuropathic pain and activate microglia. Interestingly, the type I interferons (IFNs) signal was significantly activated after astrocytes elimination, and the most activated Gene Ontology terms and pathways were associated with the type I IFNs signal which was mainly activated in microglia and further verified in vitro and in vivo. Furthermore, different concentrations of interferon and Stimulator of interferon genes (STING) agonist could activate the type I IFNs signal in microglia. These results elucidate that selectively eliminating resident astrocytes attenuated neuropathic pain associated with type I IFNs signal activation in microglia. Targeting type I IFNs signals is proven to be an effective strategy for neuropathic pain treatment after SCI.

By selecting five key operational parameters—inlet temperature, operating temperature, anode humidity, cathode humidity, and operating pressure—and using PEMFC power density, membrane temperature difference, and membrane water content as performance indicators, simulations were conducted using 3D CFD modeling and orthogonal experiments to identify the most significant factors influencing PEMFC performance and determine the optimal operational parameter combination. The results show that working pressure has the most significant impact on PEMFC performance. Pressure variations cause significant changes in diffusion and heat conduction within the PEMFC. When the working pressure increases from 1.0 MPa to 3.0 MPa, the power density increases by approximately 11.2 %, but the temperature difference within the membrane increases by about 30.5 %. The difference between operating temperature and inlet temperature directly leads to changes in the temperature difference within the membrane. Moreover, changes in operating temperature greatly affect the water content within the proton exchange membrane, which in turn impacts the PEMFC's power density. When the operating temperature increases from 60 °C to 100 °C, the water content within the membrane decreases by approximately 50.5 %, and the power density decreases by 60.4 %. By optimizing the combination of operating parameters using a comprehensive scoring method, the temperature difference within the membrane can be controlled at 27.78 °C while ensuring the power density is increased to 0.92 W/cm2.

Objectives This study aimed to investigate the changes in the incidence and mortality trends of ovarian cancer (OC), cervical cancer (CC) and uterine cancer (UC) in the Fujian Province, southeastern China.Design Provincial, population-based, retrospective observational study.Setting Fujian province, southeastern China between 2011-2020.Participants From 2011 to 2020, 6178 new cases and 2037 deaths caused by 3 gynaecological cancers were eligible for analysis.Primary and secondary outcome measures The primary outcome measures were the incidence and mortality rates, including the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR), of three gynaecological cancers. The secondary outcome measure was the prevalence (average annual per cent changes (AAPC)).Results The incidence of all three gynaecological cancers increased from 2011 to 2020. CC had the slowest upward trend, with an AAPC of 2.54% over the period. However, it had the highest ASIR among the 3 cancers in 2020 (10.41/100 000). UC showed a rapid increase, with an AAPC of 15.15% from 2016 to 2020. While the mortality rate of UC remained stable, both CC and OC also exhibited rising trends, with the CC having the highest ASMR (3.05/100 000) in 2020. The ASMR for CC increased rapidly, with the highest AAPC of 5.51%. Conversely, changes in the ASMR for UC were not statistically significant (p=0.601). Moreover, high incidence rates were more common among perimenopausal women and older participants in the respective cancer groups where the increased mortality was observed.Conclusions Gynaecological cancer burden remains a public health issue in Fujian Province, with an increasing incidence. Improving the healthcare system and promoting a healthy lifestyle should be highlighted to reduce the cancer burden.

Abstract Anti‐gamma‐aminobutyric acid receptor type A (GABAA) encephalitis is a relatively rare autoimmune encephalitis, and often associated with thymoma. Here, a 44‐year‐old female was diagnosed as having a thymoma with autoimmune encephalitis. At 4‐month follow‐up she was without recurrence of symptoms after treatment with methylprednisolone pulse therapy and immunotherapy. This case report provides a reference for the identification of this type of paraneoplastic encephalitis and for a therapeutic schedule. It also highlights that conservative treatment may be effective for patients with a tumor and GABAA encephalitis.

This article presents the results of an ongoing inventory of Ascomycota in Yunnan, China, carried out as part of the research project series “Exploring ascomycete diversity in Yunnan”. From over 100 samples collected from diverse host substrates, microfungi have been isolated, identified and are currently being documented. The primary objective of this research is to promote the discovery of novel taxa and explore the ascomycete diversity in the region, utilising a morphology-phylogeny approach. This article represents the second series of species descriptions for the project and introduces three undocumented species found in the families Bambusicolaceae, Dictyosporiaceae and Periconiaceae, belonging to the suborder Massarineae (Pleosporales, Dothideomycetes). These novel taxa exhibit typical morphological characteristics of Bambusicola, Periconia and Trichobotrys, leading to their designation as Bambusicola hongheensis, Periconia kunmingensis and Trichobotrys sinensis. Comprehensive multigene phylogenetic analyses were conducted to validate the novelty of these species. The results revealed well-defined clades that are clearly distinct from other related species, providing robust support for their placement within their respective families. Notably, this study unveils the phylogenetic affinity of Trichobotrys within Dictyosporiaceae for the first time. Additionally, the synanamorphism for the genus Trichobotrys is also reported for the first time. Detailed descriptions, illustrations and updated phylogenies of the novel species are provided, and thus presenting a valuable resource for researchers and mycologists interested in the diversity of ascomycetes in Yunnan. By enhancing our understanding of the Ascomycota diversity in this region, this research contributes to the broader field of fungal taxonomy and their phylogenetic understanding.

Abstract Purpose Neuroendocrine carcinoma of the cervix (NECC) is rare but results in poor prognosis. The causes of death (CODs) in NECC patients are rarely reported. Our study aimed to explore the distributions of death causes of NECC patients compared with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) and to develop a validated survival prediction model. Methods Patients diagnosed with NECC, SCC, or ADC were identified from the Surveillance, Epidemiology, and End Results Program database from 1975 to 2019. We analyzed the standardized mortality ratio (SMR) to determine each cause of death for each survival time category. The Kaplan–Meier method was used for survival analysis. Univariate and multivariate Cox regression analyses were used to establish a nomogram model. Results A total of 358 NECC patients were included in this study, and 270 (75.4%) died during the follow‐up period. Patients with NECC had 5.55 times (95% CI, 4.53–6.79, p

Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain.Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.

Introduction With the advancements in cancer prevention and diagnosis, the proportion of newly diagnosed early-stage cervical cancers has increased. Adjuvant therapies based on high-risk postoperative histopathological factors significantly increase the morbidity of treatment complications and seriously affect patients’ quality of life. Objectives Our study aimed to establish a diagnostic nomogram for vaginal invasion (VI) among early-stage cervical cancer (CC) that can be used to reduce the occurrence of positive or close vaginal surgical margins. Methods We assembled the medical data of early-stage CC patients between January 2013 and December 2021 from the Fujian Cancer Hospital. Data on demographics, laboratory tests, MRI features, physical examination (PE), and pathological outcomes were collected. Univariate and multivariate logistic regression analyses were employed to estimate the diagnostic variables for VI in the training set. Finally, the statistically significant factors were used to construct an integrated nomogram. Results In this retrospective study, 540 CC patients were randomly divided into training and validation cohorts according to a 7:3 ratio. Multivariate logistic analyses showed that age [odds ratio (OR) = 2.41, 95% confidence interval (CI), 1.29-4.50, P = 0.006], prognostic nutritional index (OR = 0.18, 95% CI, 0.04-0.77, P = 0.021), histological type (OR = 0.28, 95% CI, 0.08-0.94, P = 0.039), and VI based on PE (OR = 3.12, 95% CI, 1.52-6.45, P = 0.002) were independent diagnostic factors of VI. The diagnostic nomogram had a robust ability to predict VI in the training [area under the receiver operating characteristic curve (AUC) = 0.76, 95% CI: 0.70-0.82] and validation (AUC = 0.70, 95% CI: 0.58-0.83) cohorts, and the calibration curves, decision curve analysis, and confusion matrix showed good prediction power. Conclusion Our diagnostic nomograms could help gynaecologists quantify individual preoperative VI risk, thereby optimizing treatment options, and minimizing the incidence of multimodality treatment-related complications and the economic burden.

The significant increase in the number of vehicles, traffic speed, and load has significantly reduced the lifespan of pavements and increased maintenance costs. Therefore, the incorporation of polymers into bituminous binders is imperative to enhance pavement quality and performance. Nowadays, polymer-modified asphalt binders (PMBs) play a crucial role in pavement engineering. This polymer absorbs asphalt molecules to form a network connecting the entire binder, giving it better viscoelasticity than the base asphalt. Although polymers do enhance the properties of asphalt to some extent, there are still certain limitations hindering the future development of polymer-modified asphalt, such as high costs, low resistance to aging, and poor storage stability. Additionally, there is limited literature available that reviews the advantages and disadvantages of various polymer modifiers. The aim of this paper is to conduct a systematic review that evaluates the benefits and drawbacks of different polymer types in modifying asphalt materials. This comprehensive synthesis study thoroughly examines the historical evolution of polymer modified binders (PMBs) for asphalt pavement, including selection criteria for polymers used in asphalt modification, current state-of-the-art knowledge regarding the internal structure and morphology of PMBs, evaluation methodologies for PMB properties, binder specifications specific to PMBs, recommendations based on findings, and future research. This review will not only merit research from an academic perspective, but also provide guidance for pavement engineering.

Abstract Aims To present a case series of 11 rare uterine tumors resembling ovarian sex cord tumors (UTROSCTs), and review the literature on this topic to offer up-to-date treatment management for UTROSCTs. Method Eight cases from Fujian Cancer Hospital between January 2017 and May 2023 and three patients from Fujian Union Hospital between October 2012 and October 2020 were retrospectively reviewed. All cases were pathologically confirmed as UTROSCTs by two senior and experienced pathologists. Clinical behaviors, medical data, histopathological features, therapy approaches, and survival outcomes were discussed. Results The median age at initial diagnosis was 53 years (29–70 years). 3 (27.3%) patients were under 40. Seven cases presented with abnormal vaginal bleeding, one with menstrual disorder, one with abnormal vaginal secretion, and two patients were accidentally found by physical examination without any symptoms. Three patients were initially misdiagnosed with endometrial cancer by MRI. Curettage was performed in all cases. Nine of them were well diagnosed by routine curettage, except for two samples, which were identified after surgery. Immunohistochemical biomarkers, such as CD99, Desmin, WT-1, CK, Vimentin, SMA, α-Inhibin, Ki67, CD56, ER, PR, and CR, tend to be positive in UTRO SCs patients. Six patients underwent hysterectomy with bilateral salpingo-oophorectomy. Two cases received a radical hysterectomy with bilateral salpingo-oophorectomy, retroperitoneal lymph node dissection, and omentum dissection. Three UTROSCTs were under observation after mass resection. The median PFS was 24 months (range 1–125 months). Conclusion UTROSCT is a rare mesenchymal tumor with low malignant potential. Treatment modalities should be carefully considered to balance the therapy outcomes and patient needs. Surgery conservative management might be suitable for young women with fertility desires.

Abstract Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

Abstract Object This study aimed to establish an effective risk nomogram to predict the early distant metastasis (EDM) probability of cervical cancer (CC) patients treated with radical radiotherapy to aid individualized clinical decision‐making. Methods A total of 489 patients with biopsy‐confirmed CC between December 2018 and January 2021 were enrolled. Logistic regression with the stepwise backward method was used to identify independent risk factors. The nomogram efficacy was evaluated by using the area under the receiver operating characteristic curve (AUC), C‐index by 1000 bootstrap replications, etc. Finally, patients were divided into high‐ and low‐risk groups of EDM based on the cut‐off value of nomogram points. Results 36 (7.36%) CC patients had EDM, and 20 (55.6%) EDM had more than one metastatic site involved. Age below 51 (OR = 2.298, p

Milk is an ideal environment for the growth of microorganisms, especially psychrotrophic bacteria, which can survive under cold conditions and produce heat-resistant enzymes. Psychrotrophic bacteria create the great problem of spoiling milk quality and safety. Several ways that milk might get contaminated by psychrotrophic bacteria include animal health, cowshed hygiene, water quality, feeding strategy, as well as milk collection, processing, etc. Maintaining the quality of raw milk is critically essential in dairy processing, and the dairy sector is still affected by the premature milk deterioration of market-processed products. This review focused on the recent detection and control strategies of psychrotrophic bacteria and emphasizes the significance of advanced sensing methods for early detection. It highlights the ongoing challenges in the dairy industry caused by these microorganisms and discusses future perspectives in enhancing milk quality through innovative rapid detection methods and stringent processing controls. This review advocates for a shift towards more sophisticated on-farm detection technologies and improved control practices to prevent spoilage and economic losses in the dairy sector.

Abstract This paper addresses a two-stage stochastic-robust model for the day-ahead self-scheduling problem of an aggregator considering uncertainties. The aggregator, which integrates power and capacity of small-scale prosumers and flexible community-owned devices, trades electric energy in the day-ahead (DAM) and real-time energy markets (RTM), and trades reserve capacity and deployment in the reserve capacity (RCM) and reserve deployment markets (RDM). The ability of the aggregator providing reserve service is constrained by the regulations of reserve market rules, including minimum offer/bid size and minimum delivery duration. A combination approach of stochastic programming (SP) and robust optimization (RO) is used to model different kinds of uncertainties, including those of market price, power/demand and reserve deployment. The risk management of the aggregator is considered through conditional value at risk (CVaR) and fluctuation intervals of the uncertain parameters. Case studies numerically show the economic revenue and the energy-reserve schedule of the aggregator with participation in different markets, reserve regulations, and risk preferences.

ObjectivePrevious observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.MethodsWe explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results.ResultsWe found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320–2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291–2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295–1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008–1.078, p = 0.0157).ConclusionOur study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Abstract Backgrounds Platelet‐to‐albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. Methods A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms‐one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. Results Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune‐Inflammation Index (SII), platelet‐to‐lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p

Abstract Currently, there is a lack of effective treatments for spinal cord injury (SCI), a debilitating medical condition associated with enduring paralysis and irreversible neuronal damage. Extradural decompression of osseous as well as soft tissue components has historically been the principal objective of surgical procedures. Nevertheless, this particular surgical procedure fails to tackle the intradural compressive alterations that contribute to secondary SCI. Here, we propose an early intrathecal decompression strategy and evaluate its role on function outcome, tissue sparing, inflammation, and tissue stiffness after SCI. Durotomy surgery significantly promoted recovery of hindlimb locomotor function in an open‐field test. Radiological analysis suggested that lesion size and tissue edema were significantly reduced in animals that received durotomy. Relative to the group with laminectomy alone, the animals treated with a durotomy had decreased cavitation, scar formation, and inflammatory responses at 4 weeks after SCI. An examination of the mechanical properties revealed that durotomy facilitated an expeditious restoration of the injured tissue's elastic rigidity. In general, early decompressive durotomy could serve as a significant strategy to mitigate the impairments caused by secondary injury and establish a more conducive microenvironment for prospective cellular or biomaterial transplantation.

Abstract Background Vertebroplasty is the main minimally invasive operation for osteoporotic vertebral compression fracture (OVCF), which has the advantages of rapid pain relief and shorter recovery time. However, new adjacent vertebral compression fracture (AVCF) occurs frequently after vertebroplasty. The purpose of this study was to investigate the risk factors of AVCF and establish a clinical prediction model. Methods We retrospectively collected the clinical data of patients who underwent vertebroplasty in our hospital from June 2018 to December 2019. The patients were divided into a non-refracture group (289 cases) and a refracture group (43 cases) according to the occurrence of AVCF. The independent predictive factors for postoperative new AVCF were determined by univariate analysis, least absolute shrinkage and selection operator (LASSO) logistic regression, and multivariable logistic regression analysis. A nomogram clinical prediction model was established based on relevant risk factors, and the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effect and clinical value of the model. After internal validation, patients who underwent vertebroplasty in our hospital from January 2020 to December 2020, including a non-refracture group (156 cases) and a refracture group (21 cases), were included as the validation cohort to evaluate the prediction model again. Results Three independent risk factors of low bone mass density (BMD), leakage of bone cement and “O” shaped distribution of bone cement were screened out by LASSO regression and logistic regression analysis. The area under the curve (AUC) of the model in the training cohort and the validation cohort was 0.848 (95%CI: 0.786–0.909) and 0.867 (95%CI: 0.796–0.939), respectively, showing good predictive ability. The calibration curves showed the correlation between prediction and actual status. The DCA showed that the prediction model was clinically useful within the whole threshold range. Conclusion Low BMD, leakage of bone cement and “O” shaped distribution of bone cement are independent risk factors for AVCF after vertebroplasty. The nomogram prediction model has good predictive ability and clinical benefit.

Abstract Background Human epidermal growth factor receptor 2 (HER2) targeted therapy combined with endocrine therapy has been recommended as an alternative treatment strategy for patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (MBC). This study aimed to evaluate the role of pyrotinib, an oral pan-HER irreversible tyrosine kinase inhibitor, in combination with letrozole for patients with HR-positive, HER2-positive MBC. Methods In this multi-center, phase II trial, HR-positive and HER2-positive MBC patients who were not previously treated for metastasis disease were enrolled. Patients received daily oral pyrotinib 400 mg and letrozole 2.5 mg until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the clinical benefit rate (CBR) assessed by an investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results From November 2019 to December 2021, 53 patients were enrolled and received pyrotinib plus letrozole. As of August 2022, the median follow-up duration was 11.6 months (95% confidence interval [CI], 8.7–14.0 months). The CBR was 71.7% (95% CI, 57.7–83.2%), and the objective response rate was 64.2% (95% CI, 49.8–76.9%). The median progression-free survival was 13.7 months (95% CI, 10.7–18.7 months). The most common treatment-related adverse event of grade 3 or higher was diarrhea (18.9%). No treatment-related deaths were reported, and one patient experienced treatment discontinuation due to adverse event. Conclusions Our preliminary results suggested that pyrotinib plus letrozole is feasible for the first-line treatment of patients with HR-positive and HER2-positive MBC, with manageable toxicities. Trial registration ClinicalTrials.gov, NCT04407988.

Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ “reserve cells” upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.

Summary: Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mechanisms and identifying clinical targets for metabolic diseases.

Using weekly data from January 2020 to December 2021 on the prices of various links in the Chinese broiler industry chain and the COVID-19 epidemic, we employed a time-varying parametric vector auto-regressive (TVP-VAR) model to investigate the dynamic effects of public health events on price fluctuations of upstream, midstream, and downstream products in the Chinese broiler industry chain. Our findings showed that the COVID-19 epidemic had different effects on the prices of various broiler products, both in direction and magnitude, at different lags and time intervals. Chicken and live chicken prices were impacted the most, followed by broiler chick prices, while broiler feed prices were impacted the least. The epidemic constantly impacted broiler chick and chicken prices, while its effect on live chicken prices was initially negative but turned positive afterwards. Additionally, the impact of the COVID-19 epidemic on broiler product prices consistently increased with more extended lag periods. The impulse responses at different epidemic time points were heterogeneous. With the results of this study, policy recommendations can be suggested to relevant government departments to optimize the prevention and control measures for public health emergencies and ensure price stability in the broiler industry.

Background: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. Methods: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. Results: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334–3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133–3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370–0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). Conclusion: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.

Accaumulating studies focus on the effects of C3-positive A1-like phenotypes and S100A10-positive A2-like phenotypes of reactive astrocytes on spinal cord injury (SCI), however the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI remain poorly understood. Through transgenic mice and lineage tracing, we aimed to determine the origins of C3- and S100A10-positive reactive astrocytes. Meanwhile, the distribution and dynamic changes in C3- and S100A10-positive reactive astrocytes were also detected in juvenile and adult SCI mice models and cultured astrocytes. Combing with bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq) and bioinformatic analysis, we further explored the dynamic transcripts changes of C3- and S100A10-positive reactive astrocytes after SCI. We confirmed that resident astrocytes produced both C3- and S100A10-positive reactive astrocytes, whereas ependymal cells regenerated only S100A10-positive reactive astrocytes in lesion area. Importantly, C3-positive reactive astrocytes were predominantly activated in adult SCI mice, while S100A10-positive reactive astrocytes were hyperactivated in juvenile mice. Furthermore, we observed that C3- and S100A10-positive reactive astrocytes had a dynamic transformation process at different time in vitro and vivo, and a majority of intermediate states of C3- and S100A10-positive reactive astrocytes were found during transformation. RNA-seq and scRNA-seq results further confirmed that the transcripts of C3-positive reactive astrocytes and their lipid toxicity were gradually increased with time and age. In contrast, S100A10-positive reactive astrocytes transcripts increased at early time and then gradually decreased after SCI. Our results provide insight into the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI, which would be valuable resources to further target C3- and S100A10-positive reactive astrocytes after SCI.

Identifying prostate cancer patients who may respond well to PARP inhibitors is important for their success in the clinic. Here, using a genome-wide CRISPR-Cas9 knockout screen, the authors identify MMS22L as a biomarker for sensitivity to PARP inhibition in BRCA1/2-proficient prostate cancer.

ABSTRACT The emergence of various new Klebsiella pneumoniae carbapenemase (KPC) variants leading to ceftazidime-avibactam treatment failure is a new challenge in current clinical anti-infection treatment. Here, we report a ceftazidime-avibactam-resistant K. pneumoniae 1072–2 clinical strain carrying a novel KPC variant, KPC-134, which differs from KPC-2 by both single mutation (D178A) and 8-amino acid insertions (asp-asp-asn-arg-ala-pro-asn-lys). The results of antimicrobial susceptibility testing showed that the isolate was resistant to meropenem (MIC = 4 mg/L), ceftazidime (MIC ≥ 32 mg/L), cefepime (MIC ≥128 mg/L), aztreonam (MIC ≥128 mg/L), and ceftazidime-avibactam (MIC ≥128 mg/L) but sensitive to imipenem (MIC = 0.5 mg/L), imepenem-relebactam (MIC = 0.5 mg/L), meropenem-vaborbactam (MIC = 2 mg/L), and aztreonam-avibactam (MIC = 4 mg/L). The plasmid containing bla KPC-134 was isolated from K. pneumoniae, and the bla KPC-134 gene was cloned into plasmid pHSG398 and transformed into an Escherichia coli DH5α to observe changes in antimicrobial resistance. The results indicated that the transformant was positive for bla KPC-134 and increased MICs of ceftazidime-avibactam, ceftazidime, cefepime, and aztreonam by 512-fold, 256-fold, 16-fold, and 4-fold, respectively, compared with the recipient. The results of third-generation sequencing showed that the bla KPC-134 gene was carried by a 133,789 bp IncFII-IncR plasmid, and many common resistance genes (including bla CTX-M-65, bla TEM-1B, bla SHV-12, rmtB, and catB4) along with the IS26, tnpR, ISkpn8, ISkpn6-like, and Tn1721 elements were identified. IMPORTANCE The emergence of various new KPC variants leading to ceftazidime-avibactam treatment failure is a new challenge for clinical anti-infection treatment. Here, we describe the characterization of a ceftazidime-avibactam-resistant blaKPC-134-positive Klebsiella pneumoniae clinical strain for the first time. K. pneumoniae bearing with KPC variant often mislead clinical anti-infection treatment because of their unique antimicrobial susceptibility profile and the tendency of conventional carbapenemase assays to give false negative results. Therefore, timely identification of KPC variants and effective anti-infective therapy are key to saving infected patients.

Yunnan, located in southwestern China, is known for its high fungal diversity, and many of which are endemic to the region. As part of our ongoing studies on fungi in Yunnan, we introduce two new genera in Phaeothecoidiellaceae (Mycosphaerellales), to accommodate one Repetophragma-like and another Stomiopeltis-like taxa. Pseudorepetophragma gen. nov. is introduced herein as a monotypic genus to accommodate P. zygopetali comb. nov.(≡ Repetophragma zygopetali), whereas Pseudostomiopeltis gen. nov. is introduced to accommodate Ps. xishuangbannaensis gen. et sp. nov. and Ps. phyllanthi comb. nov.(≡ Stomiopeltis phyllanthi), based on a new collection from Yunnan. In addition, Stomiopeltis sinensis is transferred to Exopassalora as E. sinensis comb. nov. due to its phylogenetic affinity and grouped with E. zambiae, the generic type of Exopassalora. This study provides new insights into the biodiversity of fungal species in this region and adds to our understanding of their ecological roles, as well as the resolution to ambiguous taxa in Phaeothecoidiellaceae.

Human fungal diseases are infections caused by any fungus that invades human tissues, causing superficial, subcutaneous, or systemic diseases. Fungal infections that enter various human tissues and organs pose a significant threat to millions of individuals with weakened immune systems globally. Over recent decades, the reported cases of invasive fungal infections have increased substantially and research progress in this field has also been rapidly boosted. This review provides a comprehensive list of human fungal pathogens extracted from over 850 recent case reports, and a summary of the relevant disease conditions and their origins. Details of 281 human fungal pathogens belonging to 12 classes and 104 genera in the divisions ascomycota, basidiomycota, entomophthoromycota, and mucoromycota are listed. Among these, Aspergillus stands out as the genus with the greatest potential of infecting humans, comprising 16 species known to infect humans. Additionally, three other genera, Curvularia, Exophiala, and Trichophyton, are recognized as significant genera, each comprising 10 or more known human pathogenic species. A phylogenetic analysis based on partial sequences of the 28S nrRNA gene (LSU) of human fungal pathogens was performed to show their phylogenetic relationships and clarify their taxonomies. In addition, this review summarizes the recent advancements in fungal disease diagnosis and therapeutics.

Underwater object detection is crucial in marine exploration, presenting a challenging problem in computer vision due to factors like light attenuation, scattering, and background interference. Existing underwater object detection models face challenges such as low robustness, extensive computation of model parameters, and a high false detection rate. To address these challenges, this paper proposes a lightweight underwater object detection method integrating deep learning and image enhancement. Firstly, FUnIE-GAN is employed to perform data enhancement to restore the authentic colors of underwater images, and subsequently, the restored images are fed into an enhanced object detection network named YOLOv7-GN proposed in this paper. Secondly, a lightweight higher-order attention layer aggregation network (ACC3-ELAN) is designed to improve the fusion perception of higher-order features in the backbone network. Moreover, the head network is enhanced by leveraging the interaction of multi-scale higher-order information, additionally fusing higher-order semantic information from features at different scales. To further streamline the entire network, we also introduce the AC-ELAN-t module, which is derived from pruning based on ACC3-ELAN. Finally, the algorithm undergoes practical testing on a biomimetic sea flatworm underwater robot. The experimental results on the DUO dataset show that our proposed method improves the performance of object detection in underwater environments. It provides a valuable reference for realizing object detection in underwater embedded devices with great practical potential.

Purpose: Circulating tumor DNA (ctDNA) has good clinical guiding value for metastatic breast cancer (MBC) patients. This study aimed to apply a novel genetic analysis approach for therapeutic prediction based on ctDNA alterations. Method: This nonrandomized, multicenter study recruited 223 MBC patients (NCT05079074). Plasma samples were collected for target-capture deep sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when progressive disease (PD) was evaluated. Samples were categorized into four levels according to the number of ctDNA alterations: level 1 (no alterations), level 2 (1–2 alterations), level 3 (3–4 alterations) and level 4 (≥5 alterations). According to ctDNA alteration level and variant allele frequency (VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors (ctle-RECIST) was established to assess treatment response and predict progression-free survival (PFS). Results: The median PFS in level 1 (6.63 months) patients was significantly longer than that in level 2–4 patients (level 2: 5.70 months; level 3–4: 4.90 months, p

Piezoelectric catalysis has been considered a promising technology in water pollution control. In this report, environmental-friendly (Bi1/2Na1/2)(1-x)BaxTiO3(BNBT-x) piezoelectric materials with the morphotropic phase boundary (MPB) were prepared by one-step solvothermal method. The piezocatalytic activities of the BNBT-x piezoelectric materials were examined by the degradation of RhB dye solution. The results demonstrate that the BNBT-6 catalyst with the MPB exhibit a higher piezocatalytic performance of up to 98.95% compared to pure BNT. In addition, the BNBT-6 catalyst exhibits good reusability, which is of great significance for practical applications. This work opens a route to design and develops high-performance piezocatalysts.

BackgroundEpidemiological trends of esophageal cancer attributable to smoking remain unclear. This study aimed to estimate the spatiotemporal trends of the esophageal cancer burden attributable to smoking to assist in global esophageal cancer prevention and smoking cessation.MethodsData on esophageal cancer attributable to smoking were obtained from the Global Burden of Disease Study 2019. The number and age-standardized rates of esophageal cancer mortality (ASMR) and disability-adjusted life years (ASDR) were analyzed by age, sex, and location. Joinpoint regression analysis was used to analyze the temporal trends of esophageal cancer burden attributable to smoking over 30 years.ResultsIn 2019, the number of global esophageal cancer deaths and disability-adjusted life years (DALYs) attributable to smoking was approximately 203,000 and 475 million, respectively. The global esophageal cancer deaths and DALYs due to smoking were approximately 1.5-fold increased from 1990 to 2019, but the corresponding ASMR and ASDR had decreased. The heaviest burden occurred in East Asia, Mongolia, and the middle socio-demographic index (SDI) region. The male-to-female ratio was approximately 12.7 in the esophageal cancer deaths and DALYs and was approximately 14.3 in the ASMR and ASDR. The heaviest burden appeared in the 60–74 years age group. The estimated annual percentage change (EAPC) in ASMR was highly negatively associated with ASMR in 1990 (ρ = −0.41, p < 0.001) and SDI in 2019 (ρ = −0.29, p < 0.001).ConclusionDespite reductions in ASMR and ASDR, the esophageal cancer burden attributable to smoking remains heavy, especially in middle SDI regions. Active tobacco control can reduce esophageal cancer burden.

Two pervious concrete projects (named as SR28 and SR431), with the same mixture design but different winter maintenance activities, were included in this research. Both projects are located in the Lake Tahoe area, Nevada, United States. Testing results indicated that the mechanical properties were significantly higher in SR28 cored samples than the ones in SR431. It was found that the SR28 pieces have fewer air voids, while the SR431 samples have higher water absorption and hydraulic conductivity, and the SR28 samples show fare better performance against repeated freezing and thawing cycles than the SR431 ones. scanning electron microscope pictures of crack surfaces in cores taken from SR28 indicate that the cement binder phase has been largely retained. However, in the coring sample of SR431, needle-shaped residues can be seen within the cement binder phase and an abundance of precipitated micro-sized crystalized particles can be observed. On a micrometer scale, the μCT examination reveals that the porosity of SR28 samples is significantly less than that of SR431. The analyzing results give a clue to demonstrate the durability of pervious concrete pavement can be attributed to the construction quality control, maintenance activity, or the weather and locations of the field sites.

The traditional adaptive cruise system is responsible for delay in recognizing the cut-in/cut-out behaviour of front vehicle, and there is significant longitudinal acceleration of the vehicle fluctuation leading to reduced driver’s comfort level and even dangerous situation. In this paper, the next generation simulation data set and back propagation (BP) neural network are used to train the vehicle lane change recognition model to recognize the lane change behaviour of the preceding vehicle. The higher controller adopts variable weight linear quadratic optimal control to adjust the weight parameters according to the recognition results of front vehicle to reduce the fluctuation of vehicle acceleration. The lower layer adopts fuzzy proportional-integral-derivative (PID) control to follow the expected acceleration and builds the vehicle inverse dynamic model. Through CarSim/Simulink co-simulation, the results show that, under the cut-in or cut-out and working conditions, the behaviour of the leading vehicle can be recognized, following target can be switched in advance, weight parameters can be adjusted and the large fluctuation of longitudinal acceleration can be reduced.

Abstract Background Cancer stem cells (CSCs) are implicated in cancer progression, chemoresistance, and poor prognosis; thus, they may be promising therapeutic targets. In this study, we aimed to investigate the prognostic application of differentially expressed CSC-related genes in lung squamous cell carcinoma (LUSC). Methods The mRNA stemness index (mRNAsi)-related differentially expressed genes (DEGs) in tumors were identified and further categorized by LASSO Cox regression analysis and 1,000-fold cross-validation, followed by the construction of a prognostic score model for risk stratification. The fractions of tumor-infiltrating immune cells and immune checkpoint genes were analyzed in different risk groups. Results We found 404 mRNAsi-related DEGs in LUSC, 77 of which were significantly associated with overall survival. An eight-gene prognostic signature (PPP1R27, TLX2, ANKLE1, TIGD3, AMH, KCNK3, FLRT3, and PPBP) was identified and used to construct a risk score model. The TCGA set was dichotomized into two risk groups that differed significantly (p = 0.00057) in terms of overall survival time (1, 3, 5-year AUC = 0.830, 0.749, and 0.749, respectively). The model performed well in two independent GEO datasets (p = 0.029, 0.033; 1-year AUC = 0747, 0.783; 3-year AUC = 0.746, 0.737; 5-year AUC = 0.706, 0.723). Low-risk patients had markedly increased numbers of CD8+ T cells and M1 macrophages and downregulated immune checkpoint genes compared to the corresponding values in high-risk patients (p