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Abstract This study investigates global extreme precipitation events (EPEs) during warm seasons, with a particular focus on EPEs preceded by extreme heat stress (EPE-Hs) and a comparative analysis with those not (EPE-NHs). Using reanalysis product and Earth System Model data, the spatiotemporal characteristics and temperature sensitivities of EPEs are analyzed. Results show that EPE-Hs, while less frequent, have longer duration and greater magnitude compared to EPE-NHs, particularly in high latitude regions. In the future, a significant increase is projected in the characteristics of EPE-Hs, in contrast to the stable duration and magnitude of EPE-NHs. EPE-Hs demonstrate substantially higher temperature sensitivity than EPE-NHs, especially in low latitudes. The precipitation-temperature scaling relationships diverge markedly between EPE-Hs and EPE-NHs, with notable regional variations. These insights are pivotal for crafting region-specific early warning and adaptation strategies to mitigate the risks associated with extreme precipitation under the backdrop of global warming.

Abstract. Background:. Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. Methods:. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. Results:. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+ DCs, IFN-responding DCs, MHCII+ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+ monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Conclusions:. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup’s specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV.

Abstract Purpose In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. Methods Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. Results Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P

BackgroundFaced with cancer patients in the near-death stage, spousal caregivers may experience a series of stress reactions and have a high risk of suffering from physical and psychological problems. Good social support can help alleviate stressful reactions.ObjectivesTo investigate stress responses and social support among spouse caregivers of young and middle-aged patients with terminal cancer in the near-death stage, and to explore the death care experience of spouse caregivers.MethodsA prospective mixed-methods study was conducted. Questionnaires of stress response questionnaire and social support rating scale were used to investigate stress responses and social support of spouse caregivers. And semi-structured interviews were conducted to explore the death care experience of spouse caregivers in at a university-affiliated hospital in China.ResultsSpouse caregivers with higher social support scores were significantly more likely to have poor stress response. Meanwhile, whether the spouses had alternative care for other dependents, the number of venous pathways and instruments in/on the patient’s body significantly affected the spousal stress response. Among them, spousal social support was the best influencing factor to predict spousal stress response. Four qualitative themes of the death care experience were identified. Theme 1: Psychological feelings of spouses caregivers when they care for the patients’ physical function. Theme 2: Psychological feelings of spouse caregivers when they communicated with the patients. Theme 3: Psychological feelings of spouses caregivers when they will being widowed soon. Theme 4: The focus of life shift, and life concept change.ConclusionOverall, spousal stress response was statistically affected by alternative caregivers for spouses, spousal social support, and the number of venous pathways and instruments in/on the patient’s body. Among that, social support was the best influencing factor to predict the stress response. Meanwhile, spousal caregivers was distressed and felt deeply fear, wronged and helpless deep and when facing the patients’ dying symptoms and communicating with patient, and reflected on the essence of life, and changing the concept of life.Implications for practiceMedical staff should pay special attention to spousal caregivers’ physical discomfort and improve spousal social support, and provide targeted information and assistance to decrease spousal stress response in the near-death stage of cancer patients.

BackgroundUC patients suffer more from colorectal cancer (CRC) than the general population, which increases with disease duration. Early colonoscopy is difficult because ulcerative colitis-associated colorectal cancer (UCAC) lesions are flat and multifocal. Our study aimed to identify promising UCAC biomarkers that are complementary endoscopy strategies in the early stages.MethodsThe datasets may be accessed from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The co-expressed modules of UC and CRC were determined via weighted co-expression network analysis (WGCNA). The biological mechanisms of the shared genes were exported for analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To identify protein interactions and hub genes, a protein-protein interaction network and CytoHubba analysis were conducted. To evaluate gene expression, external datasets and experimental validation of human colon tissues were utilized. The diagnostic value of core genes was examined through receiver operating characteristic (ROC) curves. Immune infiltration analysis was employed to investigate the associations between immune cell populations and hub genes.ResultsThree crucial modules were identified from the WGCNA of UC and CRC tissues, and 33 coexpressed genes that were predominantly enriched in the NF-κB pathway were identified. Two biomarkers (CXCL1 and BCL6) were identified via Cytoscape and validated in external datasets and human colon tissues. CRC patients expressed CXCL1 at the highest level, whereas UC and CRC patients showed higher levels than the controls. The UC cohort expressed BCL6 at the highest level, whereas the UC and CRC cohorts expressed it more highly than the controls. The hub genes exhibited significant diagnostic potential (ROC curve > 0.7). The immune infiltration results revealed a correlation among the hub genes and macrophages, neutrophils and B cells.ConclusionsThe findings of our research suggest that BCL6 and CXCL1 could serve as effective biomarkers for UCAC surveillance. Additionally, they demonstrated a robust correlation with immune cell populations within the CRC tumour microenvironment (TME). Our findings provide a valuable insight about diagnosis and therapy of UCAC.

Objective To investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors. Methods A total of 213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin (Tg), and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy was evaluated 6 months post-therapy. Statistical tests were used for data comparison, and logistic regression analysis for response factors. Results Post-therapy UIC and pre-post UIC difference were significantly correlated with Tg levels but not with reaching excellent response (ER) indicated by suppression of Tg levels below 0.2 ug/L. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for the low-intermediate and high-risk groups classified by primary tumor size, invasion, metastasis, and pathological type. Conclusion Post-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

Abstract Introduction Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. Aim We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. Subjects and methods 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. Results The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P 0 0.05 ). Conclusion Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. Trial registration NCT02958111, date of registration 04-11-2016.

Scaffold materials, seed cells and growth factors are referred to as the three elements of bone tissue engineering (BTE). However, the physical properties and biocompatibility of these scaffolds and the safety and cost of their growth factors limit their clinical application. Therefore, it is critical to develop a novel scaffold modified with efficient growth factors that meets the requirements of BTE. Herein, 3D-printed poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) composite scaffolds modified with new fusion peptides, which can effectively promote the regeneration and repair of bone defects, were developed. 3D-printed PLGA/HA composite scaffolds with appropriate HA contents were prepared and had appropriate mechanical properties. In addition, the surface of the 3D-printed PLGA/HA composite scaffold was modified with new fusion peptides to provide osteogenic, antimicrobial, and angiogenesis-promoting effects. In vitro experiments showed that the fusion peptide-modified scaffolds had good biocompatibility and a certain degree of antibacterial activity. Moreover, the fusion peptide-modified scaffolds significantly improved the migration ability of BMSCs and Ea.hy926 cells, promoted the expression of osteogenesis-related factors (BMP2, RUNX2, ALP, OPN) in BMSCs, and promoted the expression of angiogenesis-related factors (VEGF and HIF-1α) in Ea.hy926 cells. In vivo experiments showed that the fusion peptide-modified scaffolds had good osteogenic ability. This study reveals considerable application potential for bone defect repair and provides a new option of scaffold material for BTE.

Abstract Background Orchidaceae is one of the largest groups of angiosperms, and most species have high economic value and scientific research value due to their ornamental and medicinal properties. In China, Chinese Cymbidium is a popular ornamental orchid with high economic value and a long history. However, to date, no detailed information on the mitochondrial genome of any species of Chinese Cymbidium has been published. Results Here, we present the complete assembly and annotation of the mitochondrial genome of Cymbidium ensifolium (L.) Sw. The mitogenome of C. ensifolium was 560,647 bp in length and consisted of 19 circular subgenomes ranging in size from 21,995 bp to 48,212 bp. The genome encoded 35 protein-coding genes, 36 tRNAs, 3 rRNAs, and 3405 ORFs. Repeat sequence analysis and prediction of RNA editing sites revealed a total of 915 dispersed repeats, 162 simple repeats, 45 tandem repeats, and 530 RNA editing sites. Analysis of codon usage showed a preference for codons ending in A/T. Interorganellar DNA transfer was identified in 13 of the 19 chromosomes, with plastid-derived DNA fragments representing 6.81% of the C. ensifolium mitochondrial genome. The homologous fragments of the mitochondrial genome and nuclear genome were also analysed. Comparative analysis showed that the GC content was conserved, but the size, structure, and gene content of the mitogenomes varied greatly among plants with multichromosomal mitogenome structure. Phylogenetic analysis based on the mitogenomes reflected the evolutionary and taxonomic statuses of C. ensifolium. Interestingly, compared with the mitogenomes of Cymbidium lancifolium Hook. and Cymbidium macrorhizon Lindl., the mitogenome of C. ensifolium lost 8 ribosomal protein-coding genes. Conclusion In this study, we assembled and annotated the mitogenome of C. ensifolium and compared it with the mitogenomes of other Liliidae and plants with multichromosomal mitogenome structures. Our findings enrich the mitochondrial genome database of orchid plants and reveal the rapid structural evolution of Cymbidium mitochondrial genomes, highlighting the potential for mitochondrial genes to help decipher plant evolutionary history.

Abstract Background Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. Results We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. Conclusions Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

Abstract The coupling capacitance between the line and the transducer cannot be ignored when making non‐contact voltage measurements on low‐voltage three‐phase power lines. This leads to an increase in the number of unknown capacitances, and the number of correlatable response voltage equations is less than the number of unknown coupling capacitances. In this paper, a simplified decoupling method is proposed based on the characteristics of triangular three‐phase lines erected in distribution areas. Firstly, the equivalent circuit measured by the voltage sensing mechanism during three‐phase operation is established, and the three‐phase line response voltage equation is derived. Secondly, this paper proposes a three‐phase line response voltage decoupling algorithm after designing the decoupling matrix. Then, this paper uses the least squares method to solve the coefficients in the equations. Finally, the three‐phase voltage fluctuations of the actual low‐voltage stations are simulated by simulation. The measured sensor voltage values are substituted into the algorithm to invert and calculate the three‐phase line voltage. The three‐phase phase error is less than 2°. The amplitude error is less than 1.77%. The experiment verifies the stability and accuracy of the proposed decoupling method.

Abstract Strict control over hematopoietic stem cell decision making is essential for healthy life‐long blood production and underpins the origins of hematopoietic diseases. Acute myeloid leukemia (AML) in particular is a devastating hematopoietic malignancy that arises from the clonal evolution of disease‐initiating primitive cells which acquire compounding genetic changes over time and culminate in the generation of leukemic stem cells (LSCs). Understanding the molecular underpinnings of these driver cells throughout their development will be instrumental in the interception of leukemia, the enabling of effective treatment of pre‐leukemic conditions, as well as the development of strategies to target frank AML disease. To this point, a number of precancerous myeloid disorders and age‐related alterations are proving as instructive models to gain insights into the initiation of LSCs. Here, we explore this myeloid dysregulation at the level of post–transcriptional control, where RNA‐binding proteins (RBPs) function as core effectors. Through regulating the interplay of a myriad of RNA metabolic processes, RBPs orchestrate transcript fates to govern gene expression in health and disease. We describe the expanding appreciation of the role of RBPs and their post–transcriptional networks in sustaining healthy hematopoiesis and their dysregulation in the pathogenesis of clonal myeloid disorders and AML, with a particular emphasis on findings described in human stem cells. Lastly, we discuss key breakthroughs that highlight RBPs and post–transcriptional control as actionable targets for precision therapy of AML.

Exopolysaccharides (EPSs), which show excellent biological activities, like anti-tumor, immune regulation, and anti-oxidation activities, have gained widespread attention. In this study, an EPS-producing Saccharomyces cerevisiae HD-01 was identified based on 18S rDNA sequence analysis and an API 20C test. The purified HD-01 EPS was obtained by gel filtration chromatography. High-performance liquid chromatography (HPLC), gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR) revealed that it was a heteropolysaccharide composed of α-1 (38.3%), α-1, 2 (17.5%), α-1, 6 (14.8%)-linked mannose and α-1, 2, 3, 6 (24.3%), α-1 (3.3%), β-1, 4 (1.8%)-linked glucose. Chemical composition and elemental analysis indicated the existence of sulfation modifications. A scanning electron microscope (SEM) and an atomic force microscope (AFM) revealed that it exhibited a flaky structure with thorn-like protrusions on the three-dimensional surface. X-ray diffraction (XRD) revealed that it was an amorphous non-crystalline substance. HD-01 EPS had great thermostability; probiotic properties; strong antioxidant properties to DPPH, ABTS, and hydroxyl; and good reducing power. The MTT, NO, and neutral red assays demonstrated that it had a great immunomodulatory effect on macrophages RAW264.7. All results suggested that the HD-01 EPS had the potential to be applied in the food and pharmaceutical fields.

Renal cell carcinoma (RCC) is a common malignant kidney tumor; however, gastric metastasis is rare. We report the case of an 82-year-old male patient who developed gastric metastasis 12 years after an initial diagnosis of RCC. The patient underwent endoscopic full-thickness resection (EFTR), and the gastric metastatic focus was successfully removed. Postoperative pathology and immunohistochemistry showed that the gastric metastasis originated from RCC. Although gastric metastasis of RCC is rare, it should be suspected in patients with a history of RCC or gastrointestinal symptoms. EFTR is associated with reduced trauma and greater retention of gastric tissue and function. It is a more appropriate choice than surgical resection; however, it requires more endoscopists.

Study area: Three headwater basins of the Tarim River Study focus: This study built upon existing knowledge by incorporating threshold melting temperatures into the Spatial Processes in Hydrology (SPHY) model and decomposing the streamflow changes into individual runoff components. Additional glacier retreat rate data were used to calibrate the improved SPHY, which provides better constrained estimates of glacier response to climate change. We employed bias-corrected simulations from Coupled Model Intercomparison Project Phase 6 (CMIP6) models to drive the improved SPHY under four future scenarios (SSP1–2.6, SSP2–4.5, SSP3–7.0, and SSP5–8.5). New hydrological insights for the region: Modeling results show accelerated glacier melt in the future, with glacier volume at the end of this century projected to be less than 20% of the current level under SSP5–8.5. Furthermore, future streamflow is expected to decrease, most notably in the Karakash River basin under the SSP1–2.6 scenario. The reduction in streamflow, mainly during the summer months, results from decreased glacier melt runoff, which cannot be offset by increased rainfall runoff. Additionally, the implementation of climate change mitigation measures could delay glacier loss, but the dominant component of runoff would still shift from current glacier melt to future rainfall. Plain language summary: Global warming accelerates the hydrological cycle, altering the temporal and spatial patterns of streamflow, especially in cold regions, such as the Tarim River Basin. Understanding future streamflow changes is important for the economic development and ecological protection of this region, which will help to manage the risk of water shortages and to plan engineering works to mitigate water shortage crises. We therefore used state-of-the-art climate simulation to project future streamflow changes over three basins of the Upper Tarim River. We found that under all future scenarios, runoff will decrease in these basins. This decrease is mainly due to glacier retreat and cannot be mitigated by anticipated increases in rainfall in the future.

With the development and application of power electronic devices in distribution stations, the power grid has frequent broadband oscillations, with characteristics such as a wide frequency range and multiple modal components, etc. However, the existing signal estimation methods cannot provide accurate parameter information due to ignoring the dynamic changes and failing to reduce the interference. Therefore, this paper proposes a broadband signal analysis method considering fundamental wave dynamics and reducing interference to achieve high-precision identification of signal parameters and provide data for applications such as wide-frequency oscillation analysis and improving power quality issues. Firstly, the variational modal decomposition extracts the waveform information of various components and the corresponding frequencies. Secondly, correct the centre frequencies and make them filter frequencies. Finally, based on the least square method, parameter estimation of broadband signals is achieved. The performance of the algorithm is verified under the situations of frequency ramp change, frequency dynamic modulation, noise, etc. The simulation results show that the proposed algorithm can estimate the parameter information of broadband signal accurately and keep the total vector error less than 3%.

Abstract Objective This study is a retrospective analysis of the prenatal genetic diagnosis results of 1408 foetuses at high risk of DMD/BMD to provide information for clinical genetic counselling. Background Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder characterized by skeletal and cardiac muscle weakness. With the deepening of disease research, some treatments have been applied in clinics. Therefore, early and accurate prenatal diagnosis can inform pregnancy choices for high-risk families. Methods A total of 1316 unrelated DMD/BMD families with confirmed genetic diagnoses were recruited from the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University. Prenatal diagnosis of 1408 high-risk foetuses was performed by MLPA and Sanger sequencing combined with STR linkage analysis for all families. Results Among the 1316 families, large deletions, duplications, and small variants of the DMD gene accounted for 70.4% (927/1316), 8.2% (108/1316), and 21.4% (281/1316), respectively. Among 1316 mothers, 863 (65.6%) were carriers, and 453 (34.4%) were not carriers. The rate of de novo variants was 34.4% (453/1316) in our study. In addition, gonadal mosaicism was observed in 11 pregnant females. Prenatal diagnosis was provided for 1408 high-risk foetuses; 282 foetuses were identified as male patients, 219 foetuses were female carriers, and the remainder had normal genetics. The results of prenatal diagnosis were consistent with the results of follow-up. Conclusions Accurate and rapid prenatal diagnosis can be achieved using MLPA, Sanger sequencing, and STR linkage analysis. Furthermore, germline mosaicism in DMD should not be ignored; considering this, a prenatal diagnosis for all pregnant women with a family history of DMD/BMD regardless of whether they carried disease-causing variants is proposed. Genetic counselling and targeted prenatal diagnosis will continue to be a cornerstone of DMD/BMD family management in the future.

ABSTRACTCanine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine.IMPORTANCEMany sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

Summary: In the tumor microenvironment (TME), tumor-associated NEs (TANs) have the potential to be protumorigenic or antitumorigenic within the TME in response to environmental cues. The diversity and plasticity of NEs (NEs) underlie the dual potential of TANs in the TME. Here, we utilized the tumor-targeting bacterium VNP20009 (VNP) to carry a plasmid expressed IFNβ (VNP-IFNβ), which can deliver IFNβ and remodel TANs to an antitumorigenic phenotype, and performed preclinical evaluations in the B16F10 lung metastasis model and the B16F10 subcutaneous xenograft model. Compared with VNP, VNP-IFNβ recruited more NEs and macrophages (Mφs) with antitumor phenotypes in lung metastases and activated dendritic cells (DCs) differentiation, which activated antitumor immune responses of CD4+ T cells, and ultimately inhibited melanoma progression. This study enriches the bacterial-mediated tumor therapy by using tumor-targeting bacteria to deliver IFNβ to the tumor site and inhibit melanoma growth and metastasis by remodeling the tumor immune microenvironment.

PurposeThis study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods and materialsOur retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a “MELODIE” multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed.ResultsAfter a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects.ConclusionLong-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.

BackgroundEnhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD.MethodsA prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate.ResultsA total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups.ConclusionsIn this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

Abstract The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations. This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry. Consequently, there is an urgent need for eco-friendly and efficient antiviral drugs that can effectively combat viruses and prevent diseases such as PEDV, PRRSV, PRV, and other viral infections. To this end, we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts (CHE) against PRV. In vitro testing of several extracts, namely, Echinacea, Ilex purpurea Hassk, Ganoderma lucidum Kars, Taraxacum mongolicum, and Ilex rotunda Thunb, exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects. Specifically, their antiviral selectivity indexes were significantly higher, with values ranging from 6- to 144-fold. The antiviral efficacy of five CHEs was evaluated against other RNA viruses, including PRRSV and PEDV. The extracts showed substantial inhibition of PEDV and PRRSV proliferation. Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects. To understand the antiviral mechanisms underlying their potent activity, a time-of-addition experiment was conducted. The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV, PEDV, and PRRSV. The study found that the Chinese herbal extracts, Echinacea and Ilex purpurea Hassk, had both direct and indirect effects on virus particles and cellular targets, demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV. These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV, PEDV and PRRSV in the swine industry. The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions. Graphical Abstract

In the contemporary context, pest detection is progressively moving toward automation and intelligence. However, current pest detection algorithms still face challenges, such as lower accuracy and slower operation speed in detecting small objects. To address this issue, this study presents a crop pest target detection algorithm, GLU-YOLOv8, designed for complex scenes based on an enhanced version of You Only Look Once version 8 (YOLOv8). The algorithm introduces the SCYLLA-IOU (SIOU) loss function, which enhances the model generalization to various pest sizes and shapes by ensuring smoothness and reducing oscillations during training. Additionally, the algorithm incorporates the Convolutional Block Attention Module (CBAM) and Locality Sensitive Kernel (LSK) attention mechanisms to boost the pest target features. A novel Gated Linear Unit CONV (GLU-CONV) is also introduced to enhance the model’s perceptual and generalization capabilities while maintaining performance. Furthermore, GLU-YOLOv8 includes a small-object detection layer with a feature map size of 160 × 160 to extract more features of small-target pests, thereby improving detection accuracy and enabling more precise localization and identification of small-target pests. The study conducted a comparative analysis between the GLU-YOLOv8 model and other models, such as YOLOv8, Faster RCNN, and RetinaNet, to evaluate detection accuracy and precision. In the Scolytidae forestry pest dataset, GLU-YOLOv8 demonstrated an improvement of 8.2% in mAP@0.50 for small-target detection compared to the YOLOv8 model, with a resulting mAP@0.50 score of 97.4%. Specifically, on the IP102 dataset, GLU-YOLOv8 outperforms the YOLOv8 model with a 7.1% increase in mAP@0.50 and a 5% increase in mAP@0.50:0.95, reaching 58.7% for mAP@0.50. These findings highlight the significant enhancement in the accuracy and recognition rate of small-target detection achieved by GLU-YOLOv8, along with its efficient operational performance. This research provides valuable insights for optimizing small-target detection models for various pests and diseases.

Lactarius hatsudake Tanaka is a mycorrhizal edible mushroom with an appealing taste and rich nutrition. It is also a significant food and has medicinal value. In this study, the plantation of L. hatsudake during the harvest period was taken as the research object, and this article explores which bacteria in the soil contribute to the production and growth of L. hatsudake. The soil of the control (CK) and the soil of the mushroom-producing area [including the soil of the base of the mushroom (JT) and the mycorrhizal root soil (JG)] was collected in the plantation. The three sites’ bacterial community structure and soil diversity were analyzed using high-throughput sequencing technology, and a molecular ecological network was built. Soil bacteria in the L. hatsudake plantation had 28 tribes, 74 classes, 161 orders, 264 families, 498 genera, and 546 species. The dominant phyla were Proteobacteria and Acidobacteria, and the dominant genera were Burkholderia_Caballeronia_Paraburkholderia, Acidothermus, Bradyrhizobium, Candidatus_Xiphinematobacter, and Granulicella. The α-diversity of soil bacteria in JT was significantly lower than that in JG and CK, and the β-diversity in JT samples was significantly different from that in JG and CK samples. The size and complexity of the constructed network were smaller in JT samples than in JG and CK samples, and the stability was higher in JT samples than in JG and CK samples. The positive correlation between species in JT samples was dominant. The potential mycorrhizal helper bacteria (MHB) species of L. hatsudake was determined using correlation and differential group analysis. The results support future research on mycorrhizal synthesis, plantation management, and the function of microorganisms in the soil rhizosphere of L. hatsudake.

A direct method for simultaneously updating mass and stiffness matrices of the undamped piezoelectric smart structural models based on incomplete modal measured data is presented. By applying the generalized singular value decomposition and some matrix derivatives, the optimal approximate mass and stiffness matrices which satisfy the required eigenvalue equation and the orthogonality relation are found under the Frobenius norm sense. The method is computationally efficient as neither iteration nor eigenanalysis is required. Numerical results are included to illustrate the effectiveness of the proposed method.

Abstract Background Urorectal septum malformation sequence (URSMS) is characterized by incomplete partitioning of the genital, rectal, and urinary tracts, resulting in a severe form of anorectal malformation. The partial URSMS, also known as the persistent cloaca, represents a milder variant where a single perineal opening serves as a passage for the urinary, gastrointestinal, and reproductive tracts. Case presentation We present a rare case of partial URSMS accompanied by duplicated vagina and uterus, hydronephrosis, ascites, and anal atresia. Conclusions This case report describes the sonographic findings at different stages of pregnancy and their changes throughout gestation.

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) is a group of rapidly progressive autosomal recessive disorders characterized by intrahepatic cholestasis. PFIC-3 is caused by mutations in the ATP-binding cassette subfamily B member 4 gene (ABCB4), which encodes multidrug resistance protein 3 (MDR3/ABCB4). Patients are usually in infancy or childhood, but cirrhosis and portal hypertension may be the first manifestation in older children or young adults. Case presentation A 25-year-old young woman with recurrent abnormal hepatic function was mainly characterized by increased gamma glutamyl transpeptidase (GGT) and bile acid with cryptogenic cirrhosis. After 7 months of treatment with ursodeoxycholic acid (UDCA), her hepatic pathology suggested there were also obvious widening and venous fibrosis around the portal vein, and slight bile duct hyperplasia at the edge of the portal area. Infiltration of inflammatory cells around the portal vein and hepatocyte ABCB4/MDR3 protein was basically normal. Sequencing indicated the patient had heterozygous mutations in the ABCB4 gene: c.2696C > G and wes [hg19]7q21.12(87032513–87033422) × 1. Through SWISS-MODEL Predict for protein structures, the missense mutation results in protein side chain missing a methyl group (-CH3), and the deletion mutation results in the serious damage to the structure of MDR3 protein which lead to phosphatidylcholine deficiency of bile in the capillary bile ducts. The toxic effect of bile salts then damages the bile ducts, causing cholestasis and cholangitis, which can then develop into biliary cirrhosis. Through the analysis of pathogenicity prediction software, the mutations led to PFIC3. After treatment of UDCA for 29 months, her cirrhosis was improved, hepatic function was close to normal. Conclusion Novel heterozygous mutations are the molecular pathological cause of PFIC3 in this patient. All young adult patients with occult cirrhosis should be tested for ABCB4. Early diagnosis of PFIC3 and continued treatment with UDCA are key to improving prognosis and delaying the onset of end-stage liver disease.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1β and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.

Radiotherapy is a commonly used method in the treatment of bladder cancers (BC). Radiation-induced immunogenic cell death (ICD) is related to the immune response against cancers and their prognoses. Even though dendritic cells (DC) act as powerful antigen-presenting cells in the body, their precise role in this ICD process remains unclear. Accordingly, an in vitro study was undertaken to ascertain whether high-dose radiation-induced ICD of BC cells could regulate the immune response of DC. The results indicated that high-dose radiation treatments of BC cells significantly increased their levels of apoptosis, blocked their cell cycle in the G2/M phase, increased their expression of ICD-related proteins, and upregulated their secretion of CCL5 and CCL21 which control the directed migration of DC. It was also noted that expression of CD80, CD86, CCR5, and CCR7 on DC was upregulated in the medium containing the irradiated cells. In conclusion, the present findings illustrate that high-dose radiation can induce the occurrence of ICD within BC cells, concomitantly resulting in the activation of DC. Such findings could be of great significance in increasing the understanding how radiotherapy of BC may work to bring about reductions in cell activity and how these processes in turn lead to immunoregulation of the function of DC.

Abstract Background BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells. Methods This study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis. Results We compared the heterogeneity of CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT+NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1βhi Mφ, S100A9hi Mφ, interferon-responsive Mφ, CD16hi Mφ, MARCO hi Mφ, and S100A11hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell–cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy. Conclusion Taken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies’ response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

Background: A hospital-based case-control study was carried out to elucidate the association of Matrix metalloproteinase-2 (MMP-2) gene candidate polymorphisms with the susceptibility to Alzheimer’s disease (AD) in the Chinese Han population. Methods: A total of 200 AD cases and an equal number of healthy controls were recruited to undergo genotyping of specific loci within the MMP-2 gene loci (rs243866, rs2285053, rs243865). Logistic regression analysis was applied to examine the association of the genotypes and alleles of MMP-2 gene polymorphisms with AD after adjusting clinical confounding factors. Results: Within AD group, a high proportion of rs243866 genotype carriers were found, and the difference remained significant despite adjusting for other clinical indicators. Among individuals with the rs243866 AA genotype and rs243865 TT genotype, the onset age of AD occurred at a younger age. Early-onset AD risk in rs243866 AA genotype carriers was 6.528 times higher than those in GG genotype carriers, and individuals with rs243865 TT genotype faced a 4.048-fold increased risk compared to those with CC genotype. Conclusions: MMP-2 gene rs243866 and rs243865 polymorphisms were closely associated with the onset age of AD. The presence of rs243866 AA genotype emerged as a crucial predictor of AD risk.

AgNbO3-based antiferroelectric ceramics can be used to prepare dielectric ceramic materials with energy storage performance. However, their efficiency is much lower than that of relaxors, which is one of the biggest obstacles for their applications. To overcome this problem, AgNbO3 ceramics co-doped with Eu3+ and Ta5+ at the A- and B-sites were prepared in this work. The Ag0.97Eu0.01Nb0.85Ta0.15O3 sample has a Wr of 6.9 J/cm3 and an η of 74.6%. The ultrahigh energy storage density and efficiency of Ag0.97Eu0.01Nb0.85Ta0.15O3 has been ascribed to the synergistic effect of the increase in the breakdown electric field, the enhancement of antiferroelectric stability, the construction of multiphase coexistence, and the modification of the domain structure morphology. The Ag0.97Eu0.01Nb0.85Ta0.15O3 ceramic is expected to be one of the options for preparing dielectric capacitors.

Abstract Oncolytic bacteria are the most promising tumor target vector. Questions also remain regarding finding a balance between the therapeutic efficacy and safety of oncolytic bacteria. The critical measure of how this balance is maintained is the improvement in tumor colonization. Attenuated Salmonella typhimurium (VNP20009) as the only Salmonella strain to be evaluated in a clinical trial is a potential tumor therapeutic bacterium. A delivery system with controlled release of VNP after being loaded into neutrophils, which significantly increases the tumor‐targeting of VNP and enhances its therapeutic efficacy in a melanoma lung metastasis model is constructed. To improve the synergistic therapeutic effect, a PD1 nanobody is applied to this system (NE(PD1nb)). NE(PD1nb) activate dendritic cells (DCs) differentiation and stimulate the M1‐like differentiation of macrophages, and induce CD4+ T‐cells maturity and cytotoxic CD8+ T‐cells activation through DCs tumor antigen presentation.

Docetaxel is one of the most commonly used drugs in prostate cancer (PCa) chemotherapy, but its therapeutic effect in PCa is usually limited due to its drug resistance. APOBEC3B is a DNA cytosine deaminase that can alter biological processes, including chemoresistance. APOBEC3B is upregulated in various cancers. However, the biological function and underlying regulation of APOBEC3B in PCa remain unclear. In this study, we explored the role of APOBEC3B in PCa chemoresistance and the molecular mechanism of its dysregulated expression. Our results revealed that APOBEC3B was upregulated in PCa docetaxel-resistant cells, while its knockdown significantly repressed cell proliferation and docetaxel resistance of PCa cells. Bioinformatics and luciferase report analysis showed that miR-138–5p targeted APOBEC3B. In addition, miR-138–5p overexpression impeded cell proliferation and docetaxel resistance in PCa, while miR-138–5p inhibitors reversed this process. Further studies showed that upregulation of APOBEC3B expression in docetaxel-resistant cells overexpressing miR-138–5p could desensitize PCa cells to docetaxel treatment. Taken together, miR-138–5p regulates PCa cell proliferation and chemoresistance by targeting the 3′-UTR of APOBEC3B, which may provide novel insights and therapeutic targets for the treatment of PCa.

Abstract Background Noninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV). Methods A retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV. Results In patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters. Conclusion SS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.

In order to expand the source of exopolysaccharides (EPS) from lactic acid bacteria, obtain EPS from lactic acid bacteria with clear source, stable yield and excellent biological characteristics. In this study, a strain of lactic acid bacteria with high EPS production was isolated and screened from self-made orange fermentation liquid by slime producing colony method. Morphological observation, 16S rDNA sequence analysis results and API 50 CHL test were combined to identify the strain. Antioxidant and milk coagulation characteristics of the lactic acid bacteria EPS were studied by antioxidant and milk coagulation test. Results showed that: A 16S rDNA fragment of Leuconostoc mesenteroides with 1444 bp was obtained, and its GenBank number was OM302141. The contents of total sugar, protein and uronic acid in strain HDE1 EPS were 41.73%±1.74%, 0.29%±0.03% and 7.69%±0.42%, respectively. The EPS showed good antioxidant activity when the concentration was 3 mg/mL. When the concentration of EPS was 5 mg/mL, the scavenging ability of DPPH, ABTS+ and H2O2- free radical reached 50.00%±0.05%, 40.00%±0.02% and more than 50%. The hydroxyl scavenging ability was 49.96%±0.03%, and the total reducing power of EPS was 38.82%±0.09%. Milk curdling results showed that HDE1 could make skim milk with 3% (w/v) sucrose coagulate completely at 36 h. These results indicated that strain HDE1 EPS had good antioxidant and milk condensation properties, showing good application potential in food, medicine and probiotics.

Clerodendrum cyrtophyllum is a common medicinal plant used by Miao people. In order to study the chemical constituents and antibacterial activities of C. cyrtophyllum in Guizhou, China. Macroporous adsorption resin, reversed phase column chromatography, silica gel column chromatography, Sephadex LH-20 column chromatagraphy, and semi-preparative high performance liquid chromatography were used to separate and purify 95% ethanol extracts from C. Cyrtophyllum. The antibacterial activities were evaluated by MTT method. The results showed 18 compounds were isolated and identified as friedelin (1), α-amyrin palmitate (2), sambuculin A (3), 22-dehydroclerosterol (4), isopetasin (5), taraxasteryl palmitate (6), stigmasterol (7), 22-dehydroclerosterol-3-O-β-D-(6′-O-margaroyl)-glucopyranoside (8), 3-O-β-D-galactopyranosyl-(24β)-ethylcholesta-5,22,25-trien (9), cistanoside D (10), tortoside F (11), balanophonin (12), luteoloside (13), acteoside (14), luteolin (15), acantrifoside E (16), trichotomside B (17), cistanoside C (18). Among of them, compounds 2, 3, 5, 6, 8-13, 16-18 were all isolated from C. cyrtophyllum for the first time. Besides, biological activity test showed Compound 13 had antibacterial activity against Streptococcus uberis. The study enriches the chemical composition of C. cyrtophyllum, and provides reference for the drug development of anti-mastitis of dairy cows.

The design of fully biological flame retardants is vital for environment-friendly and sustainability development. Herein, a fully biological hyperbranched flame retardant named PA-DAD was synthesized successfully through a simple neutralization reaction between 1,10-Diaminodecane (DAD) and phytic acid (PA). PA-DAD as a kind of reactive flame retardant was subsequently employed to composite with epoxy resin (EP). The obtained EP composite, comprising 25 wt% PA-DAD, exhibited excellent flame resistance with an appreciative limiting oxygen index (LOI) of 28.0%, and a desired V-0 rating of UL-94. The favorable attributes stem from the evident flame-retardant characteristics of PA-DAD, manifesting particularly within the gaseous and condensed phases of combustion. Benefitting from the PA-DAD with the synergetic effect of smoke suppression and flame resistance, the EP/25% PA-DAD composite displayed highlighted reductions both in smoke production and heat release rate. In contrast with neat EP, total smoke production (TSP), peak smoke production release (pSPR), the peak heat release rate (pHRR), and the rate of fire growth (FIGRA) of the EP/25% PA-DAD composite were decreased by 49.5%, 57.0%, 72.2% and 77.8%, respectively. Moreover, the EP/25% PA-DAD composite resulted in well-preserved mechanical properties, especially enhanced toughness, compared with the neat EP. The strategies in our work provided a facile, green, and highly efficient way for fabricating high fire-retardant EP composites.

According to the characteristics of massive, multi-source, heterogeneous, and rapid growth of book literature data information from the perspective of the metaverse, in order to meet the requirements of efficient management and rapid retrieval such as standardized storage, effective extraction, and scientific library construction for unstructured massive and heterogeneous book in-formation, this study focuses on the normalization of multi-source heterogeneous massive book data, the construction of a warehouse model for book data in the metaverse perspective, and the query and optimization of book data. Systematic research and implementation were conducted to solve the problem of how to process, manage, and query multi-source heterogeneous massive book data in the metaverse, improving the utilization value and query efficiency of the data. This study utilized the semi-structured features of book text data to construct an extraction rule model for heterogeneous book data, and effectively extracted massive heterogeneous book information. Based on the HBase distributed storage structure and parallel computing technology, the storage scheme has been optimized and query efficiency has been improved to ensure efficient management and retrieval of massive heterogeneous book data. The experimental results show that compared with traditional methods, there are significant improvements in multiple aspects such as the accuracy and recall rate of book text data extraction, the management methods and query efficiency of book information.

Fresh Lentinus edodes was extremely susceptible to a series of deterioration phenomena such as loss of water, nutrition and flavor, tissue browning, decay, umbrella opening and aging in the process of storage and transportation, due to its high water content, strong respiration and transpiration, microbial contamination, etc. The deterioration phenomenon mentioned above severely limited the development of the preservation industry of L. edodes. Therefore, this paper summarizes the causes of phenomena mentioned above, and also reviewes the preservation technologies on L. edodes, including physical preservation (low temperature preservation, modified atmosphere preservation, cold sterilization preservation), chemical preservation, biological preservation and compound preservation, etc. The research progress, principle and effects of these preservation technologies on L. edodes are also reviewed. The problems existing in the research of postharvest deterioration and preservation technology on L. edodes are summarized and the prospect is made. This review would provide references for the research direction of postharvest preservation technology and the development of green preservation products on L. edodes.

Abstract In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

As a green and clean source of energy, natural gas plays an indispensable role in changing the energy structure and reducing greenhouse gas emissions. In this context, forecasting natural gas production becomes particularly important. In China, natural gas production has obvious seasonal and cyclical characteristics. To this end, a grey prediction model combined with particle swarm optimization (PSO) is proposed: the PSO-based data grouping grey model with a fractional order accumulation (PSO-FDGGM (1,1)). The traditional grey model has shortcomings such as low prediction accuracy and poor adaptability, and its application is limited. Compared with the traditional grey models, this model can be used to predict time series with seasonal characteristics, and the prediction accuracy is higher. Based on the data grouping-based grey modelling method (DGGM (1,1)), this model introduces the modeling method of the grey system model with the fractional order accumulation (FGM (1,1)), that is, combining data grouping with fractional accumulation, and using PSO to optimize fractional-order parameters, which improves the performance and adaptability of the model. In order to verify the effectiveness of the model, the model is compared with the traditional grey model (GM (1,1)), FGM (1,1) model, DGGM (1,1) model, autoregressive comprehensive moving average (ARIMA) model and the PSO-based grey forecasting model (PSOGM (1,1)). The mean absolute percent errors (MAPEs) of the comparison model in the test set are 7.46%, 9.28%, 4.38%, 8.60% and 5.97% respectively, while that of PSO-FDGGM (1,1) model is only 3.19%. The results show that PSO-FDGGM (1,1) has good adaptability and prediction accuracy for seasonally fluctuating sequences. In order to further verify the effectiveness and applicability of PSO-FDGGM (1,1), this paper adopts two ways: adjusting the parameters of PSO algorithm in the new model and applying the new model to the prediction of solar power generation, and the empirical results show that the new model is effective in forecasting seasonal data. Finally, the new model is used to predict the quarterly production of natural gas in China from the third quarter of 2021 to the second quarter of 2024. The forecast results can provide a basis for formulating natural gas production plans and environmental policies.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8+ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8+ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Abstract Introduction The current challenge for the treatment of varicocele is identifying patients who could benefit the most from surgery. We aimed to develop and validate a nomogram for predicting spontaneous pregnancy following microscopic varicocelectomy in infertile men, based on a large cohort. Methods Two hundred eighty-two consecutive patients who underwent microscopic varicocelectomy from January 2018 to December 2020 were enrolled as participants in the study. Xiang Hua center (206 patients) as a development cohort. Hu Nan center (76 patients) as a validation cohort. Patient clinicopathologic data were recorded. Multivariate logistic regression was used to build a predictive model with regression coefficients. Then, backward stepwise selection was applied, and the likelihood ratio test with Akaike’s information criterion was used as the stopping rule. The performance of this predictive model was assessed for discrimination, calibration, and clinical usefulness. Results Predictors of this model included the age of female partners, diameter of veins, initial and increased total progressively motile sperm count. The model demonstrated good discrimination with an AUROC of 0.925 (p

Abstract Focal spot (light spot) at single-photon level have important applications in many fields. This report demonstrates a method for measuring focal spot size at the single-photon level indirectly. This method utilizes Silicon Photomultiplier (SiPM) as the single-photon sensitive detectors, combined with a nano-positioning stage. The approach involves one- or two-dimensional space scanning and a deconvolution operation, which enable evaluations of the size and spatial distribution of the focal spot formed by a single-photon-level pulsed laser. The results indicate that the average full width at half maximum of the focal spot is about 0.657 μm, which is close to the nominal resolution of the objective lens of the microscope (i.e. 0.42 μm). The proposed method has two key advantages: (1) it can measure focal spot at the single-photon level, and (2) the focal spot can easily be aligned with the detector because the array area of the Geiger mode avalanche photodiode (Gm-APD) cells in SiPM is usually on the order of square millimeter, and there is no need to put an optical slit, knife edge, or pinhole in front of the detector. The method described herein is applicable in weak focal spot detection related fields.

ObjectiveThis study aimed to investigate sudapyridine (WX-081) antibacterial activity against Mycobacterium abscessus in vitro and its effect on in vivo bacterial growth and host survival using a zebrafish model of M. abscessus infection.MethodsWX-081 in vitro antibacterial activity was assessed based on growth inhibition of M. abscessus standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of M. abscessus growth were assessed in vivo after fluorescently labelled bacilli and drugs were injected into zebrafish. Bacterial counts were analysed using one-way ANOVA and fluorescence intensities of zebrafish tissues were analysed and expressed as the mean ± SE. Moreover, Kaplan-Meier survival analysis was conducted to assess intergroup differences in survival of M. abscessus-infected zebrafish treated with different drug concentrations using a log-rank test, with a p value