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Meijie Xu,1 Rui Wu,1,2 Ling Zhang,1 Hong-Yan Zhu,1 Guang-Yin Xu,1,2 Wenxia Qian,1 Ping-An Zhang1,2 1Department of Respiratory and Critical Care Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, People’s Republic of China; 2Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou 215123, People’s Republic of ChinaCorrespondence: Ping-An ZhangCenter for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou 215123, People’s Republic of ChinaTel +86-15006281769Email pingan@suda.edu.cnWenxia QianDepartment Of Respiratory and Critical Care Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, People’s Republic of ChinaTel +86-13952440813Email qwx1208.happy@163.comBackground: Inflammatory pain is the most common type of pain treated clinically. However, the currently available treatments for inflammatory pain have limited effects and can cause severe side effects. The aim of this study is to describe the effect of miRNA-485-5p on osteoarthritis-related inflammatory pain.Methods: Paw withdrawal threshold (PWT) of rats was measured by von Frey filaments. The expressions of miRNA-485-5p and acid-sensing ion channel 1 (ASIC1) in the dorsal root ganglion (DRG) were measured with real-time quantitative PCR and Western blotting analysis. Fluorescent in situ hybridization and fluorescent immunohistochemistry were employed to detect expression of miRNA-485-5p, acid-sensing ion channelASIC1 and co-location of miRNA-485-5p with ASIC1.Results: The PWT of rats was significantly reduced after complete Freund’s adjuvant (CFA) injection. The miRNA-485-5p expression level clearly decreased while the ASIC1 expression level was upregulated in the L4-6 dorsal root ganglion (DRG) of CFA rats. MiRNA-485-5p and ASIC1 were co-expressed in the same DRG cells of CFA rats. Amiloride, an inhibitor of ASIC1, clearly increased the PWT of CFA rats. Further, miRNA-485-5p agomir reversed the upregulation of ASICI1 and alleviated CFA-induced mechanical hypersensitivity of CFA rats.Conclusion: These results suggest that reduced expression of miRNA-485-5p contributes to inflammatory pain through upregulating ASIC1 expression, implying a promising strategy for pain therapy.Keywords: miR-485-5p, ASIC1, dorsal root ganglion (DRG), inflammatory pain

Qiu-Xia Han,1–3,* Dong Zhang,1,* Ya-Li Zhao,4 Liang Liu,5 Jing Li,5 Fu Zhang,5 Fu-Xin Luan,5 Dong-Wei Liu,3 Zhang-Suo Liu,3 Guang-Yan Cai,1,2 Xiang-Mei Chen,1,2 Han-Yu Zhu1 1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases，Beijing Key Laboratory of Kidney Diseases, Beijing 100853, People’s Republic of China; 2Medical College, Nankai University, Tianjin 300000, People’s Republic of China; 3Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology of Zhengzhou University, Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou 450052, People’s Republic of China; 4Central Laboratory, Hainan Branch of Chinese PLA General Hospital, Sanya 572000, People’s Republic of China; 5Management Department, Hainan Branch of Chinese PLA General Hospital, Sanya 572000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Han-Yu Zhu; Xiang-Mei ChenDepartment of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +86 10 6693 7763; +86 10 6693 7748Email hanyuzhu301@126.com; xiangmeichen301@126.comPurpose: Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians.Patients and methods: In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted.Results: The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p

Rui Gao,1 Jin-Hua Liang,2 Tian-Shuo Man,2 Li Wang,2 Hua-Yuan Zhu,2 Wei Wu,2 Lei Fan,2 Jian-Yong Li,2 Tao Yang,1,* Wei Xu2,*1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workPurpose: Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival. The objective of this study was to assess the prognostic value of DM in diffuse large B-cell lymphoma (DLBCL).Methods: Five hundred and fifty-three newly diagnosed DLBCL patients whose treatments included rituximab were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Multivariate Cox regression analyses screened the prognostic risk factors in relation to progression-free survival (PFS) and cancer-specific survival (CSS). Receiver-operator characteristic curves and the corresponding areas under the curve (AUC) assessed the predictive accuracy of international prognostic index (IPI) together with DM.Results: One hundred and nine patients (19.71%) had pre-existing DM. In the propensity-matched cohort, DM was associated with unfavorable PFS and CSS in rituximab era, and it was an independent risk factor for both inferior PFS and CSS, especially in patients with age ≤60 years, IPI 0−2, B symptoms and lactate dehydrogenase ≤upper limit of normal. Prediabetics also demonstrated inferior prognostic outcomes compared to patients with no diabetic tendency. DM as one additional point to IPI had larger AUC compared with IPI alone in CSS prediction and could improve the prognostic capacity of IPI.Conclusion: The results indicate that preexisting DM is an important risk factor for survival. It could help predict life expectancy and build refined prognostication models for DLBCL.Keywords: diffuse large B-cell lymphoma, diabetes mellitus, progression-free survival, cancer-specific survival, propensity score-matched analysis

Ye Wang,1,2,* Xiao-Yuan Zi,1,* Juan Su,1 Hong-Xia Zhang,1 Xin-Rong Zhang,3 Hai-Ying Zhu,1 Jian-Xiu Li,1 Meng Yin,3 Feng Yang,3 Yi-Ping Hu,11Department of Cell Biology, 2School of Clinical Medicine, 3Department of Pharmaceuticals, Second Military Medical University, Shanghai, People's Republic of China*Authors contributed equally.Abstract: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.Keywords: nanomedicine, selective cytotoxicity, apoptosis, cell cycle arrest, mitochondrion-targeted nanomaterials

The emergence of power quality as a topical issue in power systems in the 1990s largely coincides with the huge advancements achieved in the computing technology and information theory. This unsurprisingly has spurred the development of more sophisticated instruments for measuring power quality disturbances and the use of new methods in processing and analyzing the measurements. Fourier theory was the core of many traditional techniques and it is still widely used today. However, it is increasingly being replaced by newer approaches notably wavelet transform and especially in the post-event processing of the time-varying phenomena. This paper reviews the use of wavelet transform approach in processing power quality data. The strengths, limitations, and challenges in employing the methods are discussed with consideration of the needs and expectations when analyzing power quality disturbances. Several examples are given and discussions are made on the various design issues and considerations, which would be useful to those contemplating adopting wavelet transform in power quality applications. A new approach of combining wavelet transform and rank correlation is introduced as an alternative method for identifying capacitor-switching transients.

This study aimed to investigate the feasibility of using an immortal keratinocyte cell line, HaCaT cells, to effectively deliver epidermal growth factor (EGF) in a skin substitute to treat burn wounds. The skin equivalent was constructed with human EGF (hEGF) gene modified HaCaT cells obtained through stable gene transfection; these were applied to full thickness burn wounds in a rat model. The results showed that the hEGF gene modified HaCaT cells produced more than 390ng/l of bioactive hEGF in the culture supernatant. K19 and integrin-[beta]1 as keratinocyte differentiation markers were elevated in the hEGF gene modified HaCaT cells which were shown to be non-tumorigenic. The skin equivalent constructed with hEGF gene modified HaCaT cells demonstrated improved epidermal morphogenesis with a thick and compact epidermis. Wound healing was accelerated noticeably when applied with this skin substitute seeded with hEGF gene modified HaCaT cells in vivo. The results suggest that HaCaT cells modified with hEGF gene might be promising seed cells for construction of genetically modified skin substitute which can effectively secrete hEGF to accelerate wound repair and regeneration. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the diagnostic value of the airway post-processing technique of multi-slice spiral CT(MSCT) in Accessory cardiac bronchus(ACB)and to improve the understanding of this disease. Methods: The original MSCT axial images and various post-processing reconstructed images of 9 ACB cases were retrospectively analyzed.Airway post-processing techniques, including multi-planar reformation(MPR), minimum intensity projection (MinIP), volume rendering technique(VRT), CT virtual endoscopy(CTVE) and tissue transition projection (TTP), were employed. Three-dimensional recombination images of bronchial trees were obtained and classified according to the Mangiulea classification. Results: Among the 9 cases with ACB, there were 6 cases of accessory-lobed type, 3 cases of long diverticular type, and no cases of short diverticular type. The lateral axial images, MPR, MinIP, VRT, CTVE, and TTP all clearly displayed ACB. Among the 6 cases of accessory-lobed type, there were 5 cases with accessory lobe dysplasia and one case with pneumonia in an accessory lobe;One case was complicated with accessory lobe emphysema. Among the 3 cases with long diverticular type ACB, one had pneumonia. Among the 9 cases, there was 1 case with old tuberculous focus, 1 case with pulmonary fibrous focus, 1 case with pleural thickening and adhesion, and 1 case with tracheal diverticulum. Conclusion: The airway post-processing technique of MSCT can not only clarify the diagnosis, origin and classification of ACB, but also measure the opening diameter, length and distance to the tracheal carina of ACB.It guides clinical treatment and tracheoscopy, etc, and can be used as the preferred examination method for ACB.

Neutrophil proteinase 3 (PR3), cathepsin G, elastase, and neutrophil serine protease 4 constitute the neutrophil serine protease family. These four members share varying sequence homology and functional similarities with each other. However, PR3 stands out as a unique autoantigen, serving as a primary autoantigen in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Numerous studies have documented or reviewed the molecular pathogenesis or diagnostic utility of PR3 in ANCA-associated vasculitis. Nevertheless, the role of PR3 in other areas, particularly within the hematopoietic system, appears to have been overlooked. Indeed, beyond its involvement in vasculitis, PR3 contributes to cell apoptosis, hematopoietic abnormalities, diabetic ketoacidosis, and various other inflammatory diseases. In this study, we aim to summarize the research on the function of neutrophil PR3 in hematopoiesis and to elucidate its potential role in neutrophil aging and inflammatory diseases., Competing Interests: Declarations. Ethical approval: Not applicable. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy. Methods: A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors. Results: The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR =18.00, 95% CI 1.56-207.45, P =0.020) and bone marrow suppression ( OR =18.00, 95% CI 1.38-235.69, P =0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P >0.05). Conclusions: PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Background: The primary adverse effect of chemotherapy drugs is the induction of spermatogenic disorders. Schisandra chinensis (Turcz) Baill. have been preliminarily shown to have a significant ameliorative in spermatogenic disorders. Nevertheless, there are relatively few studies on non-medicinal parts such as stems of S. chinensis, which have good therapeutic potential for side effects caused by cisplatin. Up to now, a total of 238 compounds have been isolated and identified from the vine stem of S. chinensi. The main components are lignans, polysaccharides, volatile oils, and organic acids. Therefore, the development of S. chinensis stem as a source of a novel chemotherapy drug protector is of great significance., Methods: In the present study, we explored the protective effect of the stem extract of S. chinensis (SCE) against cisplatin-induced spermatogenic disorders and its possible molecular mechanisms in vitro and in vivo. The network pharmacology was used to predict the targets that may act on spermatogenic disorders. Mice were injected intraperitoneally with cisplatin at 2 mg/kg for 7 days to induce spermatogenic disorders. SCE (75, 150, and 300 mg/kg) was administered to mice by gavage for 21 days. TM3 cells were treated with Schisandrol B (Sol B) (0.5, 1, and 2 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated., Results: 16 constituents and target proteins were predicted to have possible effects on spermatogenic disorders by network pharmacology. Both in vivo and in vitro experiments showed a favorable protective effect of SCE against cisplatin-induced spermatogenic disorders. Sol B might as the major chemical component is responsibility for the protective effect. The mechanism may involve the regulation of Nrf2\HO-1 protein, PI3K\Akt, apoptosis, and MAPK signaling pathway to modulate 17βHSD, cycp450, Star and other crucial proteins in the testosterone synthesis pathway. Ultimately, this regulatory process aims to ameliorate the disruption of sex hormone secretion by cisplatin., Conclusion: These results indicated that the lignans in SCE could effectively improve the spermatogenesis barrier caused by cisplatin. These findings provided a theoretical basis for the development of non-medicinal parts of S. chinensis, and laid a foundation for improving spermatogenesis disorders caused by chemotherapy drugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Patients with sub-acute cerebral venous sinus thrombosis experience (SA.CVST) severe symptoms compared to two other venous sinus-related diseases, including chronic cerebral venous sinus thrombosis (C.CVST) and idiopathic intracranial hypertension (IIH)., Objective: This study aimed to determine whether the different immune reactions in different venous sinuses are related., Methods: Stagnant blood in the cerebral venous sinuses was extracted by passing a microcatheter and CD14 -positive cells were sorted by magnetic beads and subjected to RNA-seq sequencing., Results: Compared to patients with IIH, 128 genes were significantly down-regulated and 373 genes were significantly up-regulated in the sub-acute CVST samples. The functions of these genes were mainly focused on "immune response", "T cell activation" and "plasma membrane". Gene Set Enrichment Analysis (GSEA) showed T cell survival and activation-related function significantly unregulated in sub-acute CVST. On the other hand, there were 366 genes down-regulated in chronic CVST and 75 genes up-regulated in chronic CVST. In functional annotation, these differently expressed genes were enriched in the "extracellular region", "chemokine-mediated signaling pathway" and "immune response". GSEA analysis confirmed that chemokine-related functions were all up-regulated in sub-acute CVST and monocyte-macrophage adhesion functions were also significantly up-regulated., Conclusion: This study suggested the CD14 -positive created an activated immune response in sub-acute CVST., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chang, Song, Zhu, Zhang, Fu, Wang, Dong, Jiang, Mo and Zhang.)

In the survey of yeast diversity in high-temperature Daqu, which is a fermentation starter for Chinese sauce-flavoured Baijiu, six yeast strains representing one novel species of the genus Starmerella were isolated from samples of Daqu and surrounding environments collected in Zunyi city, Guizhou Province, China. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domains of the large subunit rRNA gene indicate that these six strains are conspecific with three other strains isolated from flowers and duckweed collected in Samoa, India and Thailand. The representative strain QFC-8 of the new species differs from the closet species Starmerella caucasica resolved by the D1/D2 sequence analysis by 13 (3.1 %, 12 substitutions and 1 gap) and 40 (10.3 %, 9 substitutions and 31 gaps) mismatches in the D1/D2 domain and ITS region, respectively. The results suggest that the novel group represents an undescribed species in the genus Starmerella , for which the name Starmerella fangiana sp. nov. is proposed. The holotype strain is CGMCC 2.7773.

Baicalin (BA), a natural component found in many traditional Chinese medicines, exerts protective effects against several viruses. Although our previous studies have revealed that the anti-hepatitis B virus (anti-HBV) activity of BA depends on hepatocyte nuclear factor (HNF) signaling, the specific mechanisms remain unclear. The present study explored the potential signaling mechanisms involved in BA-mediated HBV suppression. Transcriptomic analysis suggested that BA significantly modulates the estrogen receptor (ER) and AMPK signaling pathways in HepG2 cells. The ER alpha (ERα) binding affinity of BA and its estrogen-like agonist activity were subsequently verified through molecular docking assays, BA-ERα affinity detection experiments, ERα luciferase reporter gene assays, and qRT-PCR. ERα knockdown (shRNA) and AMPK inhibition (Compound C and doxorubicin [Dox]) experiments revealed that the sequential activation of the ERα-LKB1-AMPK-HNF signaling axis is essential for the anti-HBV effects of BA. This study indicates that BA may trigger the ERα-AMPKα-HNF pathway to inhibit HBV replication, providing insights into its potential protective mechanisms against other viruses., (© 2024. The Author(s).)

Objective: To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China. Methods: Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People's Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model. Results: The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR =2.15, 95% CI 1.24- 3.73, P =0.006), diabetes ( OR =2.09, 95% CI 1.05-4.20, P =0.037), chronic hepatitis B ( OR =2.91, 95% CI 1.30-6.51, P =0.010), CLL progressive ( OR =3.79, 95% CI 1.57-9.15, P =0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR =2.79, 95% CI 1.35-5.77, P =0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR =2.98, 95% CI 1.10-8.10, P =0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR =0.38, 95% CI 0.16-0.90, P =0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P <0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P <0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions: A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.

Medium-temperature Daqu (MT-Daqu) serves as a crucial saccharifying and fermentation agent in the production of strong-flavor Baijiu. Due to the spatial heterogeneity of solid fermentation, significant differences occurred in the fermentation state and appearance features in different parts of Daqu during fermentation. Currently, the understanding of the underlying mechanism behind this phenomenon remains limited. Here, we analyzed the microbial succession and assembly models and driving factors in different parts of MT-Daqu at the species level based on the PacBio single-molecule real-time sequencing technology. The results showed significantly different bacterial and fungal community compositions, successions, and interaction patterns in different parts of MT-Daqu. The bacterial community composition and succession model in the middle layer were similar to those in the core layer, whereas the fungal community composition and succession model in the surface layer were similar to those in the middle layer. The co-occurrence network analysis showed that microbial interaction is stronger in the middle and core layers than in the surface layer. Analyses based on both niche theory and neutral theory models indicated that deterministic processes predominantly governed the microbial community assembly and these processes played an increasingly important role from the surface to the core layer. Random forest analysis revealed that temperature was the primary endogenous factor driving the bacterial and fungal community assembly. The results of this study contribute to a better understanding of the microbial community in MT-Daqu and are helpful for the quality control of MT-Daqu fermentation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z =-13.785 and -20.822, both P <0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ 2 =6.512, 4.965, 25.115, and 46.004, all P <0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z =-8.529 and -11.235, both P <0.001).

Human polo-like kinase 1 (PLK1) has been recognized as an attractive therapeutic target against nasopharyngeal carcinoma (NPC). The kinase contains a conserved polo-box domain (PBD) that exhibits a wide specificity across various substrates. Previously, we explored natural amino acid preference in PLK1 PBD-binding phosphopeptides. However, limited to the short sequence only natural amino acids cannot guarantee the sufficient exploitation of chemical and structural diversity of the phosphopeptides. Here, we described a genetic optimization (GO) strategy to systematically optimize a 10 4 -sized 6-mer phosphopeptide array towards increasing affinity to PLK1 PBD domain by using 20 natural plus 34 unnatural amino acids as basic building blocks. A QSAR predictor was created to guide the GO optimization and then evaluated rigorously at molecular and cellular levels. Three unnatural phosphopeptides uPP8, uPP15 and uPP20 were designed as potent binders with K d = 0.18, 0.42 and 0.08 μM, respectively, in which the uPP20 also possessed a good anti-tumor activity against human NPC cells when fused with cell permeation sequence. In addition, we defined a relaxed 6-mer motif for the preferential PLK1 PBD-binding phosphosites, namely [Φ/П]-3-[ζ]-2-[ζ]-1-[pT/pS]0-[Φ/П]+1-[Φ]+2, where the symbols Φ, ζ and П represent hydrophobic, polar and aromatic amino acid types, respectively.  .

Background: Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective effect on ischemic heart injury. However, the specific mechanism by which it exerts the protective effect remains unclear. This study was designed to investigate the role of SEVO in myocardial I/R injury and its potential molecular mechanisms., Methods: Blood samples were collected from patients with acute myocardial infarction (AMI) (n = 20) and healthy volunteers (n = 20). The human cardiomyocytes AC16 models of I/R injury were induced by hypoxia/reoxygenation. The mRNA expression levels of growth differentiation factor 11 ( GDF11 ) in the cells and blood were determined by reverse transcription quantitative real-time PCR (RT-qPCR). The cell proliferation was detected by Cell Counting Kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to detect the levels of inflammatory factors interleukin (IL)-8, IL-1β and IL-6 in the cells. And biochemical assay kits were applied for the measurement of the activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the malondialdehyde (MDA) level in the cells. Moreover, western blot was employed to evaluate the levels of the p-serine-threonine protein kinase (AKT), AKT, and phosphatidylinositol 3-kinase (PI3K), protein expression in the cells., Results: The GDF11 expression was decreased in the blood of AMI patients and cardiomyocytes induced by I/R ( p < 0.01). Besides, 1% SEVO was presented to promote cardiomyocyte proliferation, inhibit apoptosis, oxidative stress and inflammation, and activate the PI3K/AKT signaling pathway through up-regulation of GDF11 expression ( p < 0.01)., Conclusion: SEVO promotes proliferation and inhibits inflammatory response, apoptosis, and oxidative stress of I/R-treated cardiomyocytes by elevating GDF11 expression, thereby reducing myocardial I/R injury. Notably, the mechanism underlying the alleviation of the I/R injury may involve the activation of PI3K/AKT signaling pathway.

The surface plasmon resonance (SPR) biosensor technology is a novel optical analysis method for studying intermolecular interactions. Owing to in-depth research on traditional Chinese medicine (TCM) in recent years, comprehensive and specific identification of components and target interactions has become key yet difficult tasks. SPR has gradually been used to analyze the active components of TCM owing to its high sensitivity, strong exclusivity, large flux, and real-time monitoring capabilities. This review sought to briefly introduce the active components of TCM and the principle of SPR, and provide historical and new insights into the application of SPR in the analysis of the active components of TCM., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the pursuit of efficient singlet oxygen generation in Fenton-like catalysis, the utilization of single-atom catalysts (SACs) emerges as a highly desired strategy. Here, a discovery is reported that the single-atom Fe coordinated with five N-atoms on N-doped porous carbon, denoted as Fe-N 5 /NC, outperform its counterparts, those coordinated with four (Fe-N 4 /NC) or six N-atoms (Fe-N 6 /NC), as well as state-of-the-art SACs comprising other transition metals. Thus, Fe-N 5 /NC exhibits exceptional efficacy in activating peroxymonosulfate for the degradation of organic pollutants. The coordination number of N-atoms can be readily adjusted by pyrolysis of pre-assembly structures consisting of Fe 3+ and various isomers of phenylenediamine. Fe-N 5 /NC displayed outstanding tolerance to environmental disturbances and minimal iron leaching when incorporated into a membrane reactor. A mechanistic study reveals that the axial ligand N reduces the contribution of Fe-3d orbitals in LUMO and increases the LUMO energy of Fe-N 5 /NC. This, in turn, reduces the oxophilicity of the Fe center, promoting the reactivity of *OO intermediate-a pivotal step for yielding singlet oxygen and the rate-determining step. These findings unveil the significance of manipulating the oxophilicity of metal atoms in single-atom catalysis and highlight the potential to augment Fenton-like catalysis performance using Fe-SACs., (© 2024 Wiley‐VCH GmbH.)

The effect on acetabular management in developmental dysplasia of the hip (DDH) patients aged 7 or older with modified low Dega osteotomy procedure was evaluated. Patients between 7 and 14 years old were managed with modified low Dega osteotomy and open reduction and concomitant procedures to evaluate whether low level osteotomy improved the clinical and radiologic outcomes after treatment. Clinical status was assessed using the modified McKay's criteria; radiologic evaluations were assessed for the modified Severin classification, the mean acetabular index (AI), Sharp angle and center-edge (CE) angle. And occurrence of triradiate cartilage injury and complications was recorded. Forty-two DDH patients (57 hips) between 7 and 14 years old were managed with modified low Dega osteotomy. The results demonstrated the latest follow-up 43 hips (75.4%) were rated excellent and 10 hips (17.5%) rated good according to the modified McKay criteria and 41 hips (71.9%) were rated excellent and 11 hips (19.3%) rated good according to Modified Severin classification, respectively. The mean Hip Score improved from 69.53 ± 7.14 before the operation to 93.17 ± 8.43 at the final follow-up. The mean AI changed from 31.9° to 20.2°, mean Sharp angle decreased from 59.3° to 38.8° and mean CE angle increased from -10.9° to 35.2°, preoperatively and at latest follow-up, respectively. The modified low Dega osteotomy combined with open reduction and concomitant procedures were found to be adequate in improving instant and sustained clinical and radiographic outcomes for the late detected pediatric walking DDH patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale : CD39, a key ectonucleotidase that drives adenosine production, acts as a critical immunosuppressive checkpoint in cancer. Although it has shown promise as a therapeutic target, clinical trials are demonstrating the need for more potent targeting approaches. This need is driving innovation towards the development of novel antibodies and the exploration of strategic combinations with a range of immunotherapies. Methods : An anti-CD39 nanobody was screened and tested for its affinity and binding ability using biolayer interferometry, ELISA and flow cytometry. Blocking ability against soluble and membrane-bound CD39 was measured after CD39 blockade. Internalization was detected using immunofluorescence. The reversal of T-cell function by the anti-CD39 antibody was assessed by CFSE-based T-cell proliferation, CD25 expression and IFN-γ secretion. The in vivo function of tumor growth inhibition was further tested in a mouse model and we also tested the phenotype of immune cells after CD39 antibody administration from tumor tissue, draining lymph nodes and peripheral blood. We inserted the antibody sequence into the chimeric antigen receptor (CAR) construct to induce MSLN CAR-T cells to secret the CD39 antibody, and the efficacy was measured in xenograft models of ovarian cancer. Results : We screened human CD39 antibodies using a VHH library and developed a single-epitope anti-CD39 nanobody, named huCD39 mAb, with high affinity and potent binding and blocking ability. The huCD39 mAb was internalized in a time-dependent manner. The in vitro study revealed that the huCD39 mAb was highly effective in enhancing T-cell proliferation and functionality. In vivo , the huCD39 mAb showed significant anti-tumor efficacy in an immunocompetent mouse model. Flow cytometry analysis demonstrated downregulated CD39 expression in immune cells after antibody administration. We also observed increased CD39 expression in ovarian cancer tissue and in activated CAR T cells. Subsequently, we developed a type of MSLN CAR-T cells secreting huCD39 mAb which showed effective eradication or inhibition in ovarian tumor xenografts. Conclusions : A novel huCD39 mAb with strong blocking ability against human CD39 and potent inhibition of tumor growth has been developed. Furthermore, a modified huCD39 mAb-secreting CAR-T cell has been generated, exhibiting superior efficacy against ovarian cancer. This provides a promising strategy for optimizing immunotherapies in ovarian cancer and potentially other malignancies., Competing Interests: Competing Interests: Yu-Chen Zhang, Xian-Yang Li, Qi Deng, Yan-Jun Ge, Rui-Rong Yi, Hua-Jing Wang, Jian-Tao Wang, Hui Zhou, Xue-Feng Kong, Rong-Jiao Liu, Xiao-Pei Li, Xiao-Wen He are employed by OriCell Therapeutics Co. Ltd., and Xiao-Pei Li, Xiao-Wen He, Qi Deng, Xian-Yang Li, Hua-Jing Wang, Yu-Chen Zhang are inventors of a patent application (CN2023106525341) related to anti-CD39 antibody. Other authors declare no competing interests., (© The author(s).)

Glucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Primary liver cancer is one of the most lethal malignancies in the world. Traditional treatment methods have limitations in terms of efficacy and safety. Radiofrequency ablation (RFA) guided by B-ultrasound, as a minimally invasive treatment, has attracted increasing attention in the treatment of primary liver cancer in recent years., Aim: To study the efficacy and safety of RFA were compared with those of traditional surgery (TS) for treating small liver cancer., Methods: At least 2 people were required to search domestic and foreign public databases, including foreign databases such as EMBASE, PubMed and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure database, China Biomedical Literature database, Wanfang database and VIP database. Controlled trials of RFA vs conventional surgery for small liver cancer were retrieved from January 2008 to January 2023. They were screened and evaluated according to the quality evaluation criteria in the Cochrane Handbook of Systematic Reviews. The meta-analysis was performed using RevMan 5.3 software., Results: A total of 10 studies were included in this study, including 1503 patients in the RFA group and 1657 patients in the surgery group. The results of the meta-analysis showed that there was no significant difference in 1-year overall survival between the two groups ( P > 0.05), while the 3-year and 5-year overall survival rates and 1-year, 3-year and 5-year tumor-free survival rates in the surgery group were greater than those in the RFA group ( P < 0.05). In terms of complications, the incidence of complications in the RFA group was lower than that in the surgery group ( P < 0.05)., Conclusion: In terms of long-term survival, TS is better than RFA for small liver cancer patients. However, RFA has fewer complications and is safer., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this work, a highly efficient rongalite/iodine-mediated oxime formation reaction for the preparation of thiohydroximic acids from methyl ketones by employing copper nitrate as the [NO] reagent has been developed. Notably, copper nitrate participated as both a catalyst and the mild oximation reagent in the transformation. This reaction is highly efficient and facile, with a broad substrate scope, especially for fused ring skeleton substrates, heterocyclic skeleton substrates, and acetyl-substituted natural products. Mechanistic studies revealed that copper nitrate might be converted into a NO 2 radical or the NO 2 radical dimeric forms as an ion-pair equivalent to participate in the transformation.

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1β secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1β, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1β, cleaved IL-1β, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 μmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1β, cleaved IL-1β, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Background and Aims: Some plants germinate their seeds enclosed by a pericarp, whereas others lack the outer packaging. As a maternal tissue, the pericarp might impart seeds with different germination strategies. Plants in a community with different flowering times might separately disperse and germinate their seeds; therefore, flowering time can be considered as one manifestation of maternal effects on the offspring. The mass of the seed is another important factor influencing germination and represents the intrinsic resource of the seed that supports germination. Using seeds from a species-rich alpine meadow located in the Hengduan Mountains of China, a global biodiversity hotspot, we aimed to illustrate whether and how the type of seed (with or without a pericarp) modulates the interaction of flowering time and seed mass with germination., Methods: Seeds were germinated in generally favourable conditions, and the speed of germination [estimated by mean germination time (MGT)] was calculated. We quantified the maternal conditions by separation of flowering time for 67 species in the meadow, of which 31 produced seeds with pericarps and 36 yielded seeds without pericarps. We also weighed 100 seeds of each species to assess their mass., Key Results: The MGT varied between the two types of seeds. For seeds with pericarps, MGT was associated with flowering time but not with seed mass. Plants with earlier flowering times in the meadow exhibited more rapid seed germination. For seeds without a pericarp, the MGT depended on seed mass, with smaller seeds germinating more rapidly than larger seeds., Conclusions: The distinct responses of germination to flowering time and seed mass observed in seeds with and without a pericarp suggest that germination strategies might be mother-reliant for seeds protected by pericarps but self-reliant for those without such protection. This new finding improves our understanding of seed germination by integrating ecologically mediated maternal conditions and inherent genetic properties., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pituitary stalk interruption syndrome (PSIS) is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes. It is characterized by a deficiency in anterior pituitary hormones, such as growth hormone, gonadotropins, and thyroid hormones. Due to the syndrome's rarity and nonspecific manifestations, there is a lack of standardized treatment strategies. Consequently, early diagnosis through imaging and on-time intervention are crucial for improving patients' outcomes., Case Summary: A 30-year-old man presented with absent secondary sexual characteristics and azoospermia. Laboratory evaluation revealed a deficiency in gonadotropins, while thyroid function was mostly within normal ranges. Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis, hypoplasia of the anterior pituitary, and ectopic posterior pituitary, leading to the diagnosis of PSIS. Initially, the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics. Pulsatile gonadotropin-releasing hormone therapy was then administered, resulting in the detection of sperm in the semen analysis within 3 mo. After 6 mo, routine semen tests showed normal semen quality. The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination, which was unsuccessful. They also attempted in vitro fertilization, but unfortunately, the woman experienced a miscarriage 10 wk after the embryo transfer., Conclusion: Early detection, accurate diagnosis, and timely treatment are crucial in improving the quality of life and fertility of PSIS patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)